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Ott, David E., Lori V. Coren, Tracy D. Gagliardi, and Kunio Nagashima. "Heterologous Late-Domain Sequences Have Various Abilities To Promote Budding of Human Immunodeficiency Virus Type 1." Journal of Virology 79, no. 14 (July 2005): 9038–45. http://dx.doi.org/10.1128/jvi.79.14.9038-9045.2005.
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ABSTRACT Retroviral late (L) domains present within Gag act in conjunction with cellular proteins to efficiently release virions from the surface of the cell. Three different critical core sequences have been identified as required elements for L-domain function: PPPY, PTAP (also PSAP), and YPDL, with different retroviruses utilizing one or two of these core sequences. The human immunodeficiency virus type 1 (HIV-1) L domain is centered around a PTAP sequence in the p6 region of Gag. To assess the ability of heterologous L-domain sequences to be functionally interchanged for those in full-length HIV-1, we produced a series of constructs that replaced PTAP-containing p6Gag sequences with those of PPPY- or YPDL-based L domains. While previous studies had found that L domains are interchangeable in other retroviruses, most of the sequences introduced into p6Gag failed to substitute for PTAP-mediated L-domain function. One exception was the 11-amino-acid p2b sequence of Rous sarcoma virus (RSV) Gag, which could fully restore HIV-1 budding, while a PPPPY sequence exchange alone did not. This suggests that the RSV L domain consists of more than simply its core L-domain sequence. The HIV-p2b chimera was as infectious as the wild type, produced normal virions, and was sensitive to proteasome inhibitors. These results show that L-domain sequences are not necessarily interchangeable. Thus, HIV-1 Gag might have a more stringent requirement for L-domain function than the other retroviruses previously studied.
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Patnaik, Akash, and John W. Wills. "In Vivo Interference of Rous Sarcoma Virus Budding by cis Expression of a WW Domain." Journal of Virology 76, no. 6 (March 15, 2002): 2789–95. http://dx.doi.org/10.1128/jvi.76.6.2789-2795.2002.
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ABSTRACT For all enveloped viruses, the actual mechanism by which nascent virus particles separate or “pinch off” from the cell surface is largely unknown. In the case of retroviruses, the Gag protein drives the budding process, and the virus release step is directed by the late (L) assembly domain within Gag. A PPPPY motif within the L domain of Rous sarcoma virus (RSV) was previously characterized as being critical for the release of virions and shown to interact in vitro with the WW domain of Yes-associated protein (Yap). To determine whether WW domain-L domain interactions can occur in vivo, we attempted to interfere with the host cell machinery normally recruited to the site of budding by inserting this WW domain in different locations within Gag. At a C-terminal location, the WWYap domain had no effect on budding, suggesting that the intervening I domains (which provide the major region of Gag-Gag interaction) prevent its access to the L domain. When positioned on the other side of the I domains closer to the L domain, the WWYap domain resulted in a dramatic interference of particle release, and confocal microscopy revealed a block to budding on the plasma membrane. Budding was restored by attachment of the heterologous L domain of human immunodeficiency virus type 1 Gag, which does not bind WWYap. These findings suggest that cis expression of WW domains can interfere with RSV particle release in vivo via specific, high-affinity interactions at the site of assembly on the plasma membrane, thus preventing host factor accessibility to the L domain and subsequent virus-cell separation. In addition, they suggest that L domain-specific host factors function after Gag proteins begin to interact.
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Martin-Serrano, Juan, David Perez-Caballero, and Paul D. Bieniasz. "Context-Dependent Effects of L Domains and Ubiquitination on Viral Budding." Journal of Virology 78, no. 11 (June 1, 2004): 5554–63. http://dx.doi.org/10.1128/jvi.78.11.5554-5563.2004.
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ABSTRACT Many enveloped viruses encode late assembly domains, or L domains, that facilitate virion egress. PTAP-type L domains act by recruiting the ESCRT-I (endosomal sorting complex required for transport I) component Tsg101, and YPXL/LXXLF-type L domains recruit AIP-1/ALIX, both of which are class E vacuolar protein sorting (VPS) factors, normally required for the generation of vesicles within endosomes. The binding cofactors for PPXY-type L domains have not been unambiguously resolved but may include Nedd4-like ubiquitin ligases. Largely because they act as autonomous binding sites for host factors, L domains are generally transferable and active in a context-independent manner. Ebola virus matrix protein (EbVP40) contains two overlapping L-domain motifs within the sequence ILPTAPPEYMEA. Here, we show that both motifs are required for efficient EbVP40 budding. However, upon transplantation into two different retroviral contexts, the relative contributions of the PTAP and PPEY motifs differ markedly. In a murine leukemia virus carrying the EbVP40 sequence, both motifs contributed to overall L domain activity, and budding proceeded in a partly Tsg101-independent manner. Conversely, when transplanted into the context of human immunodeficiency virus type 1 (HIV-1), EbVP40 L-domain activity was entirely due to a PTAP-Tsg101 interaction. In fact, a number of PPXY-type L domains were inactive in the context of HIV-1. Surprisingly, PTAP and YPXL-type L domains that simulated HIV-1 budding reduced the amount of ubiquitin conjugated to Gag, while inactive PPXY-type L domains increased Gag ubiquitination. These observations suggest that active L domains recruit deubiquitinating enzymes as a consequence of class E VPS factor recruitment. Moreover, context-dependent L-domain function may reflect distinct requirements for host functions during the morphogenesis of different viral particles or the underlying presence of additional, as yet undiscovered L domains.
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Li, Feng, Chaoping Chen, Bridget A. Puffer, and Ronald C. Montelaro. "Functional Replacement and Positional Dependence of Homologous and Heterologous L Domains in Equine Infectious Anemia Virus Replication." Journal of Virology 76, no. 4 (February 15, 2002): 1569–77. http://dx.doi.org/10.1128/jvi.76.4.1569-1577.2002.
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ABSTRACT We have previously demonstrated by Gag polyprotein budding assays that the Gag p9 protein of equine infectious anemia virus (EIAV) utilizes a unique YPDL motif as a late assembly domain (L domain) to facilitate release of the budding virus particle from the host cell plasma membrane (B. A. Puffer, L. J. Parent, J. W. Wills, and R. C. Montelaro, J. Virol. 71:6541-6546, 1997). To characterize in more detail the role of the YPDL L domain in the EIAV life cycle, we have examined the replication properties of a series of EIAV proviral mutants in which the parental YPDL L domain was replaced by a human immunodeficiency virus type 1 (HIV-1) PTAP or Rous sarcoma virus (RSV) PPPY L domain in the p9 protein or by proviruses in which the parental YPDL or HIV-1 PTAP L domain was inserted in the viral matrix protein. The replication properties of these L-domain variants were examined with respect to Gag protein expression and processing, virus particle production, and virus infectivity. The data from these experiments indicate that (i) the YPDL L domain of p9 is required for replication competence (assembly and infectivity) in equine cell cultures, including the natural target equine macrophages; (ii) all of the functions of the YPDL L domain in the EIAV life cycle can be replaced by replacement of the parental YPDL sequence in p9 with the PTAP L-domain segment of HIV-1 p6 or the PPPY L domain of RSV p2b; and (iii) the assembly, but not infectivity, functions of the EIAV proviral YPDL substitution mutants can be partially rescued by inclusions of YPDL and PTAP L-domain sequences in the C-terminal region of the EIAV MA protein. Taken together, these data demonstrate that the EIAV YPDL L domain mediates distinct functions in viral budding and infectivity and that the HIV-1 PTAP and RSV PPPY L domains can effectively facilitate these dual replication functions in the context of the p9 protein. In light of the fact that YPDL, PTAP, and PPPY domains evidently have distinct characteristic binding specificities, these observations may indicate different portals into common cellular processes that mediate EIAV budding and infectivity, respectively.
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Kimura, Yoko, Mirai Tanigawa, Junko Kawawaki, Kenji Takagi, Tsunehiro Mizushima, Tatsuya Maeda, and Keiji Tanaka. "Conserved Mode of Interaction between Yeast Bro1 Family V Domains and YP(X) n L Motif-Containing Target Proteins." Eukaryotic Cell 14, no. 10 (July 6, 2015): 976–82. http://dx.doi.org/10.1128/ec.00091-15.
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ABSTRACT Yeast Bro1 and Rim20 belong to a family of proteins which possess a common architecture of Bro1 and V domains. Alix and His domain protein tyrosine phosphatase (HD-PTP), mammalian Bro1 family proteins, bind YP(X) n L ( n = 1 to 3) motifs in their target proteins through their V domains. In Alix, the Phe residue, which is located in the hydrophobic groove of the V domain, is critical for binding to the YP(X) n L motif. Although the overall sequences are not highly conserved between mammalian and yeast V domains, we show that the conserved Phe residue in the yeast Bro1 V domain is important for binding to its YP(X) n L-containing target protein, Rfu1. Furthermore, we show that Rim20 binds to its target protein Rim101 through the interaction between the V domain of Rim20 and the YPIKL motif of Rim101. The mutation of either the critical Phe residue in the Rim20 V domain or the YPIKL motif of Rim101 affected the Rim20-mediated processing of Rim101. These results suggest that the interactions between V domains and YP(X) n L motif-containing proteins are conserved from yeast to mammalian cells. Moreover, the specificities of each V domain to their target protein suggest that unidentified elements determine the binding specificity.
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Strack, Bettina, Arianna Calistri, and Heinrich G. Göttlinger. "Late Assembly Domain Function Can Exhibit Context Dependence and Involves Ubiquitin Residues Implicated in Endocytosis." Journal of Virology 76, no. 11 (June 1, 2002): 5472–79. http://dx.doi.org/10.1128/jvi.76.11.5472-5479.2002.
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ABSTRACT Retroviral Gag polyproteins contain regions that promote the separation of virus particles from the plasma membrane and from each other. These Gag regions are often referred to as late assembly (L) domains. The L domain of human immunodeficiency virus type 1 (HIV-1) is in the C-terminal p6 gag domain and harbors an essential P(T/S)APP motif, whereas the L domains of oncoretroviruses are in the N-terminal half of the Gag precursor and have a PPXY core motif. We recently observed that L domains induce the ubiquitination of a minimal HIV-1 Gag construct and that point mutations which abolish L domain activity prevent Gag ubiquitination. In that study, a peptide from the Ebola virus L domain with overlapping P(T/S)APP and PPXY motifs showed exceptional activity in promoting Gag ubiquitination and the release of virus-like particles. We now show that a substitution which disrupts the PPXY motif but leaves the P(T/S)APP motif intact abolishes L domain activity in the minimal Gag context, but not in the context of a near full-length HIV-1 Gag precursor. Our results reveal that the P(T/S)APP motif does not function autonomously and indicate that the HIV-1 nucleocapsid-p1 region, which is proximal to p6 gag , can cooperate with the conserved L domain core motif. We have also examined the effects of ubiquitin mutants on virus-like particle production, and the results indicate that residues required for the endocytosis function of ubiquitin are also involved in virus budding.
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Ching, G. Y., and R. K. Liem. "Analysis of the roles of the head domains of type IV rat neuronal intermediate filament proteins in filament assembly using domain-swapped chimeric proteins." Journal of Cell Science 112, no. 13 (July 1, 1999): 2233–40. http://dx.doi.org/10.1242/jcs.112.13.2233.
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Type IV neuronal intermediate filament proteins consist of alpha-internexin, which can self-assemble into filaments and the neurofilament triplet proteins, which are obligate heteropolymers, at least in rodents. These IF proteins therefore provide good systems for elucidating the mechanism of intermediate filament assembly. To analyze the roles of the head domains of these proteins in contributing to their differential assembly properties, we generated chimeric proteins by swapping the head domains between rat alpha-internexin and either rat NF-L or NF-M and examined their assembly properties in transfected cells that lack their own cytoplasmic intermediate filament network. Lalphaalpha and Malphaalpha, the chimeric proteins generated by replacing the head domain of alpha-internexin with those of NF-L and NF-M, respectively, were unable to self-assemble into filaments. In contrast, alphaLL, a chimeric NF-L protein generated by replacing the head domain of NF-L with that of alpha-internexin, was able to self-assemble into filaments, whereas MLL, a chimeric NF-L protein containing the NF-M head domain, was unable to do so. These results demonstrate that the alpha-internexin head domain is essential for alpha-internexin's ability to self-assemble. While coassembly of Lalphaalpha with NF-M and coassembly of Malphaalpha with NF-L resulted in formation of filaments, coassembly of Lalphaalpha with NF-L and coassembly of Malphaalpha with NF-M yielded punctate patterns. These coassembly results show that heteropolymeric filament formation requires that one partner has the NF-L head domain and the other partner has the NF-M head domain. Thus, the head domains of rat NF-L and NF-M play important roles in determining the obligate heteropolymeric nature of filament formation. The data obtained from these self-assembly and coassembly studies provide some new insights into the mechanism of intermediate filament assembly.
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Kansas, GS, KB Saunders, K. Ley, A. Zakrzewicz, RM Gibson, BC Furie, B. Furie, and TF Tedder. "A role for the epidermal growth factor-like domain of P-selectin in ligand recognition and cell adhesion." Journal of Cell Biology 124, no. 4 (February 15, 1994): 609–18. http://dx.doi.org/10.1083/jcb.124.4.609.
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The selectin family of adhesion molecules mediates the initial interactions of leukocytes with endothelium. The extracellular region of each selectin contains an amino-terminal C-type lectin domain, followed by an EGF-like domain and multiple short consensus repeat units (SCR). Previous studies have indirectly suggested a role for each of the extracellular domains of the selectins in cell adhesion. In this study, a panel of chimeric selectins created by exchange of domains between L- and P-selectin was used to directly examine the role of the extracellular domains in cell adhesion. Exchange of only the lectin domains between L- and P-selectin conferred the adhesive and ligand recognition functions of the lectin domain of the parent molecule. However, chimeric selectins which contained both the lectin domain of L-selectin and the EGF-like domain of P-selectin exhibited dual ligand-binding specificity. These chimeric proteins supported adhesion both to myeloid cells and to high endothelial venules (HEV) of lymph nodes and mesenteric venules in vivo. Exchange of the SCR domains had no detectable effect on receptor function or specificity. Thus, the EGF-like domain of P-selectin may play a direct role in ligand recognition and leukocyte adhesion mediated by P-selectin, with the lectin plus EGF-like domains collectively forming a functional ligand recognition unit.
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Yarotskyy, Viktor, Guofeng Gao, Blaise Z. Peterson, and Keith S. Elmslie. "Domain III regulates N-type (CaV2.2) calcium channel closing kinetics." Journal of Neurophysiology 107, no. 7 (April 1, 2012): 1942–51. http://dx.doi.org/10.1152/jn.00993.2011.
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CaV2.2 (N-type) and CaV1.2 (L-type) calcium channels gate differently in response to membrane depolarization, which is critical to the unique physiological functions mediated by these channels. We wondered if the source for these differences could be identified. As a first step, we examined the effect of domain exchange between N-type and L-type channels on activation-deactivation kinetics, which were significantly different between these channels. Kinetic analysis of chimeric channels revealed N-channel-like deactivation for all chimeric channels containing N-channel domain III, while activation appeared to be a more distributed function across domains. This led us to hypothesize that domain III was an important regulator of N-channel closing. This idea was further examined with R-roscovitine, which is a trisubstituted purine that slows N-channel deactivation by exclusively binding to activated N-channels. L-channels lack this response to roscovitine, which allowed us to use N-L chimeras to test the role of domain III in roscovitine modulation of N-channel deactivation. In support of our hypothesis, all chimeric channels containing the N-channel domain III responded to roscovitine with slowed deactivation, while those chimeric channels with L-channel domain III did not. Thus a combination of kinetic and pharmacological evidence supports the hypothesis that domain III is an important regulator of N-channel closing. Our results support specialization of gating functions among calcium channel domains.
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Le Blanc, Isabelle, Marie-Christine Prévost, Marie-Christine Dokhélar, and Arielle R. Rosenberg. "The PPPY Motif of Human T-Cell Leukemia Virus Type 1 Gag Protein Is Required Early in the Budding Process." Journal of Virology 76, no. 19 (October 1, 2002): 10024–29. http://dx.doi.org/10.1128/jvi.76.19.10024-10029.2002.
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ABSTRACT Domains required late in the virus budding process (L domains) have been identified in the Gag proteins of a number of retroviruses. Here we show that the human T-cell leukemia virus type 1 candidate L domain motif PPPY is indeed required for virus production. Strikingly, however, mutation of this motif arrested virus particles at an earlier stage in the budding process than was seen for mutation of the L domain motifs thus far described for retroviruses. In view of the exchangeability of such domains, we propose that the retrovirus budding process may involve a continuum from bud formation to membrane fission.
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Tritschler, Felix, Ana Eulalio, Vincent Truffault, Marcus D. Hartmann, Sigrun Helms, Steffen Schmidt, Murray Coles, Elisa Izaurralde, and Oliver Weichenrieder. "A Divergent Sm Fold in EDC3 Proteins Mediates DCP1 Binding and P-Body Targeting." Molecular and Cellular Biology 27, no. 24 (October 8, 2007): 8600–8611. http://dx.doi.org/10.1128/mcb.01506-07.
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ABSTRACT Members of the (L)Sm (Sm and Sm-like) protein family are found across all kingdoms of life and play crucial roles in RNA metabolism. The P-body component EDC3 (enhancer of decapping 3) is a divergent member of this family that functions in mRNA decapping. EDC3 is composed of a N-terminal LSm domain, a central FDF domain, and a C-terminal YjeF-N domain. We show that this modular architecture enables EDC3 to interact with multiple components of the decapping machinery, including DCP1, DCP2, and Me31B. The LSm domain mediates DCP1 binding and P-body localization. We determined the three-dimensional structures of the LSm domains of Drosophila melanogaster and human EDC3 and show that the domain adopts a divergent Sm fold that lacks the characteristic N-terminal α-helix and has a disrupted β4-strand. This domain remains monomeric in solution and lacks several features that canonical (L)Sm domains require for binding RNA. The structures also revealed a conserved patch of surface residues that are required for the interaction with DCP1 but not for P-body localization. The conservation of surface and of critical structural residues indicates that LSm domains in EDC3 proteins adopt a similar fold that has separable novel functions that are absent in canonical (L)Sm proteins.
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Popova, Elena, Sergei Popov, and Heinrich G. Göttlinger. "Human Immunodeficiency Virus Type 1 Nucleocapsid p1 Confers ESCRT Pathway Dependence." Journal of Virology 84, no. 13 (April 28, 2010): 6590–97. http://dx.doi.org/10.1128/jvi.00035-10.
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ABSTRACT To facilitate the release of infectious progeny virions, human immunodeficiency virus type 1 (HIV-1) exploits the Endosomal Sorting Complex Required for Transport (ESCRT) pathway by engaging Tsg101 and ALIX through late assembly (L) domains in the C-terminal p6 domain of Gag. However, the L domains in p6 are known to be dispensable for efficient particle production by certain HIV-1 Gag constructs that have the nucleocapsid (NC) domain replaced by a foreign dimerization domain to substitute for the assembly function of NC. We now show that one such L domain-independent HIV-1 Gag construct (termed ZWT) that has NC-p1-p6 replaced by a leucine zipper domain is resistant to dominant-negative inhibitors of the ESCRT pathway that block HIV-1 particle production. However, ZWT became dependent on the presence of an L domain when NC-p1-p6 was restored to its C terminus. Furthermore, when the NC domain was replaced by a leucine zipper, the p1-p6 region, but not p6 alone, conferred sensitivity to inhibition of the ESCRT pathway. In an authentic HIV-1 Gag context, the effect of an inhibitor of the ESCRT pathway on particle production could be alleviated by deleting a portion of the NC domain together with p1. Together, these results indicate that the ESCRT pathway dependence of HIV-1 budding is determined, at least in part, by the NC-p1 region of Gag.
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CALDERWOOD, DAVID A., DANNY S. TUCKWELL, and MARTIN J. HUMPHRIES. "Specificity of integrin l-domain-ligand binding." Biochemical Society Transactions 23, no. 4 (November 1, 1995): 504S. http://dx.doi.org/10.1042/bst023504s.
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Jouini, Abdellatif, and Pierre Gilles Lemarié-Rieusset. "Wavelet bases on the L-shaped domain." Physica D: Nonlinear Phenomena 254 (July 2013): 12–17. http://dx.doi.org/10.1016/j.physd.2013.03.006.
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Brunotte, L., M. Lelke, M. Hass, K. Kleinsteuber, B. Becker-Ziaja, and S. Gunther. "Domain Structure of Lassa Virus L Protein." Journal of Virology 85, no. 1 (October 27, 2010): 324–33. http://dx.doi.org/10.1128/jvi.00721-10.
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Peng, Chih-Wen, Alberto J. Napuli, and Valerian V. Dolja. "Leader Proteinase of Beet Yellows Virus Functions in Long-Distance Transport." Journal of Virology 77, no. 5 (March 1, 2003): 2843–49. http://dx.doi.org/10.1128/jvi.77.5.2843-2849.2003.
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ABSTRACT The 66-kDa leader proteinase (L-Pro) of the Beet yellows virus (BYV) possesses a nonconserved N-terminal domain and a conserved, papain-like C-terminal domain. Previous work revealed that the N-terminal domain functions in RNA amplification, whereas the C-terminal domain is required for autoproteolysis. Alanine-scanning mutagenesis was applied to complete the functional analysis of L-Pro throughout the virus life cycle. This analysis indicated that the C-terminal domain of L-Pro, in addition to being required for proteolysis, also functions in RNA amplification and that these two functions are genetically separable. Examination of the role of L-Pro in BYV cell-to-cell movement revealed that none of the 20 examined replication-competent mutants was movement defective. In contrast, six of the L-Pro mutations affected the long-distance transport of BYV to various degrees, whereas three mutations completely abolished the transport. Because these mutations were located throughout the protein molecule, both domains of L-Pro function in virus transport. We conclude that in addition to previously identified functions of L-Pro, it also serves as the BYV long-distance transport factor.
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Ayoub, Nabieh, Idit Goldshmidt, and Amikam Cohen. "Position Effect Variegation at the Mating-Type Locus of Fission Yeast: A cis-Acting Element Inhibits Covariegated Expression of Genes in the Silent and Expressed Domains." Genetics 152, no. 2 (June 1, 1999): 495–508. http://dx.doi.org/10.1093/genetics/152.2.495.
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Abstract Schizosaccharomyces pombe switches its mating type by transposing a copy of unexpressed genes from the respective mat2 or mat3 cassettes to mat1. The donor cassettes are located in a silent domain that is separated from the expressed mat1 cassette by the L region. We monitored the expression of ade6 from sites in the L region and examined the relationship between the expression state at these sites and at sites within the silent domain. Results indicate that: (1) the silent domain extends into the L region, but repression is gradually alleviated with increasing distance from mat2, and overexpression of swi6 enhances PEV in the L region; (2) a transcriptionally active chromatin state, associated with reporter gene expression in the L region, spreads toward the silent domain; (3) a cis-acting element, located at the junction between the L region and mat2-P, ensures repression in the silent domain, regardless of the expression state in the L region; and (4) repression in mat1-P cells is less stringently controlled than in mat1-M cells. We discuss the functional organization of the mat region and genetic elements that ensure separation between repressed and derepressed domains.
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Lindholm, Agneta, Andreas Smeds, and Airi Palva. "Receptor Binding Domain of Escherichia coli F18 Fimbrial Adhesin FedF Can Be both Efficiently Secreted and Surface Displayed in a Functional Form in Lactococcus lactis." Applied and Environmental Microbiology 70, no. 4 (April 2004): 2061–71. http://dx.doi.org/10.1128/aem.70.4.2061-2071.2004.
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ABSTRACT Adherence of F18 fimbrial Escherichia coli to porcine intestinal epithelial cells is mediated by the adhesin (FedF) of F18 fimbriae. In a previous study, we demonstrated the specificity of the amino acid residues between 60 and 109 as the receptor binding domain of FedF. In this study, different expression, secretion, and anchoring systems for the receptor binding domain of the FedF adhesin in Lactococcus lactis were evaluated. Two partially overlapping receptor binding domains (42 and 62 amino acid residues) were expressed as fusions with L. lactis subsp. cremoris protein PrtP for evaluation of secretion efficiency. To evaluate the cell surface display of these FedF-PrtP fusions, they were further combined with different lengths of PrtP spacers fused with either the L. lactis AcmA anchor or the PrtP cell wall binding domain. An HtrA-defective L. lactis NZ9000 mutant was constructed to determine its effect on the level of secreted or anchored fusion proteins. Recombinant L. lactis clones secreting the receptor binding domain of F18 fimbriae as a fusion with the H domains of L. lactis protein PrtP were first constructed by using two different signal peptides. FedF-PrtP fusions, directed by the signal sequence of L. brevis SlpA, were throughout found to be secreted at significantly higher quantities than corresponding fusions with the signal peptide of L. lactis Usp45. In the surface display systems tested, the L. lactis AcmA anchor performed significantly better, particularly in the L. lactis NZ9000ΔhtrA strain, compared to the L. lactis PrtP anchor region. Of the cell surface display constructs with the AcmA anchor, only those with the longest PrtP spacer regions resulted in efficient binding of recombinant L. lactis cells to porcine intestinal epithelial cells. These results confirmed that it is possible to efficiently produce the receptor binding domain of the F18 adhesin in a functionally active form in L. lactis.
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Samel, Stefan A., Paul Czodrowski, and Lars-Oliver Essen. "Structure of the epimerization domain of tyrocidine synthetase A." Acta Crystallographica Section D Biological Crystallography 70, no. 5 (April 30, 2014): 1442–52. http://dx.doi.org/10.1107/s1399004714004398.
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Tyrocidine, a macrocyclic decapeptide fromBacillus brevis, is nonribosomally assembled by a set of multimodular peptide synthetases, which condense two D-amino acids and eight L-amino acids to produce this membrane-disturbing antibiotic. D-Phenylalanine, the first amino acid incorporated into tyrocidine, is catalytically derived from enzyme-bound L-Phe by the C-terminal epimerization (E) domain of tyrocidine synthetase A (TycA). The 1.5 Å resolution structure of the cofactor-independent TycA E domain reveals an intimate relationship to the condensation (C) domains of peptide synthetases. In contrast to the latter, the TycA E domain uses an enlarged bridge region to plug the active-site canyon from the acceptor side, whereas at the donor side a latch-like floor loop is suitably extended to accommodate the αIII helix of the preceding peptide-carrier domain. Additionally, E domains exclusively harbour a conserved glutamate residue, Glu882, that is opposite the active-site residue His743. This active-site topology implies Glu882 as a candidate acid–base catalyst, whereas His743 stabilizes in the protonated state a transient enolate intermediate of the L↔D isomerization.
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Grgacic, Elizabeth V. L. "Identification of structural determinants of the first transmembrane domain of the small envelope protein of duck hepatitis B virus essential for particle morphogenesis." Journal of General Virology 83, no. 7 (July 1, 2002): 1635–44. http://dx.doi.org/10.1099/0022-1317-83-7-1635.
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The envelope of duck hepatitis B virus (DHBV) consists of the small (S) and large (L) envelope proteins, which share a common C-terminal multispanning transmembrane region but differ by the long N-terminal pre-S domain of L, which is essential for interactions with both the receptor and nucleocapsid. To achieve these dual functions, L acquires mixed topologies through S-dependent post-translational translocation of its pre-S domain. This study has examined the role of S in this unusual mechanism of translocation by analysis of the α-helical transmembrane domains and their potential to engage in lateral interactions for envelope assembly. Through mutagenesis in constructs expressing the S and L envelope proteins independently, transmembrane domain 1 was identified as an essential structural determinant in S. Two polar residues in this helix were identified as contributing to L protein translocation through the assembly of S into particles, implying that the topological switch of L is part of the assembly and maturation process. The same domain in L was shown to be dispensable for L translocation and assembly, suggesting that transmembrane domain 1 of L and S have different functional roles and structural arrangements on the assembled particle. The conservation in all hepadnavirus envelope proteins of two polar residues at positions 24 and 27 of transmembrane domain 1, the former positively charged, points to this being a common determinant in particle morphogenesis for all hepadnaviruses.
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Ma, Yicong, Sajal K. Ghosh, Sambhunath Bera, Zhang Jiang, Christian M. Schlepütz, Evguenia Karapetrova, Laurence B. Lurio, and Sunil K. Sinha. "Anomalous partitioning of water in coexisting liquid phases of lipid multilayers near 100% relative humidity." Physical Chemistry Chemical Physics 18, no. 2 (2016): 1225–32. http://dx.doi.org/10.1039/c5cp04703j.
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Barrett, J., M. J. Birrer, G. J. Kato, H. Dosaka-Akita, and C. V. Dang. "Activation domains of L-Myc and c-Myc determine their transforming potencies in rat embryo cells." Molecular and Cellular Biology 12, no. 7 (July 1992): 3130–37. http://dx.doi.org/10.1128/mcb.12.7.3130.
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Members of the Myc family of proteins share a number of protein motifs that are found in regulators of gene transcription. Conserved stretches of amino acids found in the N-terminal transcriptional activation domain of c-Myc are required for cotransforming activity. Most of the Myc proteins contain the basic helix-loop-helix zipper (bHLH-Zip) DNA-binding motif which is also required for the cotransforming activity of c-Myc. L-Myc, the product of a myc family gene that is highly amplified in many human lung carcinomas, was found to cotransform primary rat embryo cells with an activated ras gene. However, L-Myc cotransforming activity was only 1 to 10% of that of c-Myc (M. J. Birrer, S. Segal, J. S. DeGreve, F. Kaye, E. A. Sausville, and J. D. Minna, Mol. Cell. Biol. 8:2668-2673, 1988). We sought to determine whether functional differences between c-Myc and L-Myc in either the N-terminal or the C-terminal domain could account for the relatively diminished L-Myc cotransforming activity. Although the N-terminal domain of L-Myc could activate transcription when fused to the yeast GAL4 DNA-binding domain, the activity was only 5% of that of a comparable c-Myc domain. We next determined that the interaction of the C-terminal bHLH-Zip region of L-Myc or c-Myc with that of a Myc partner protein, Max, was equivalent in transfected cells. A Max expression vector was found to augment the cotransforming activity of L-Myc as well as that of c-Myc. In addition, a bacterially synthesized DNA-binding domain of L-Myc, like that o c-Myc, heterodimerizes with purified Max protein to bind the core DNA sequence CACGTG. To determine the region of L-Myc responsible for its relatively diminished cotransforming activity, we constructed chimeras containing exons 2 (constituting activation domains) and 3 (constituting DNA-binding domains) of c-Myc fused to those of L-Myc. The cotransforming potencies of these chimeras were compared with those of full-length L-Myc of c-Myc in rat embryo cells. The relative cotransforming activities suggest that the potencies of the activation domains determine the cotransforming efficiencies for c-Myc and L-Myc. This correlation supports the hypothesis that the Myc proteins function in neoplastic cotransformation as transcription factors.
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Barrett, J., M. J. Birrer, G. J. Kato, H. Dosaka-Akita, and C. V. Dang. "Activation domains of L-Myc and c-Myc determine their transforming potencies in rat embryo cells." Molecular and Cellular Biology 12, no. 7 (July 1992): 3130–37. http://dx.doi.org/10.1128/mcb.12.7.3130-3137.1992.
Full textAbstract:
Members of the Myc family of proteins share a number of protein motifs that are found in regulators of gene transcription. Conserved stretches of amino acids found in the N-terminal transcriptional activation domain of c-Myc are required for cotransforming activity. Most of the Myc proteins contain the basic helix-loop-helix zipper (bHLH-Zip) DNA-binding motif which is also required for the cotransforming activity of c-Myc. L-Myc, the product of a myc family gene that is highly amplified in many human lung carcinomas, was found to cotransform primary rat embryo cells with an activated ras gene. However, L-Myc cotransforming activity was only 1 to 10% of that of c-Myc (M. J. Birrer, S. Segal, J. S. DeGreve, F. Kaye, E. A. Sausville, and J. D. Minna, Mol. Cell. Biol. 8:2668-2673, 1988). We sought to determine whether functional differences between c-Myc and L-Myc in either the N-terminal or the C-terminal domain could account for the relatively diminished L-Myc cotransforming activity. Although the N-terminal domain of L-Myc could activate transcription when fused to the yeast GAL4 DNA-binding domain, the activity was only 5% of that of a comparable c-Myc domain. We next determined that the interaction of the C-terminal bHLH-Zip region of L-Myc or c-Myc with that of a Myc partner protein, Max, was equivalent in transfected cells. A Max expression vector was found to augment the cotransforming activity of L-Myc as well as that of c-Myc. In addition, a bacterially synthesized DNA-binding domain of L-Myc, like that o c-Myc, heterodimerizes with purified Max protein to bind the core DNA sequence CACGTG. To determine the region of L-Myc responsible for its relatively diminished cotransforming activity, we constructed chimeras containing exons 2 (constituting activation domains) and 3 (constituting DNA-binding domains) of c-Myc fused to those of L-Myc. The cotransforming potencies of these chimeras were compared with those of full-length L-Myc of c-Myc in rat embryo cells. The relative cotransforming activities suggest that the potencies of the activation domains determine the cotransforming efficiencies for c-Myc and L-Myc. This correlation supports the hypothesis that the Myc proteins function in neoplastic cotransformation as transcription factors.
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Martin-Serrano, Juan, Trinity Zang, and Paul D. Bieniasz. "Role of ESCRT-I in Retroviral Budding." Journal of Virology 77, no. 8 (April 15, 2003): 4794–804. http://dx.doi.org/10.1128/jvi.77.8.4794-4804.2003.
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ABSTRACT Retroviral late-budding (L) domains are required for the efficient release of nascent virions. The three known types of L domain, designated according to essential tetrapeptide motifs (PTAP, PPXY, or YPDL), each bind distinct cellular cofactors. We and others have demonstrated that recruitment of an ESCRT-I subunit, Tsg101, a component of the class E vacuolar protein sorting (VPS) machinery, is required for the budding of viruses, such as human immunodeficiency virus type 1 (HIV-1) and Ebola virus, that encode a PTAP-type L domain, but subsequent events remain undefined. In this study, we demonstrate that VPS28, a second component of ESCRT-I, binds to a sequence close to the Tsg101 C terminus and is therefore recruited to the plasma membrane by HIV-1 Gag. In addition, we show that Tsg101 exhibits a multimerization activity. Using a complementation assay in which Tsg101 is artificially recruited to sites of HIV-1 assembly, we demonstrate that the integrity of the VPS28 binding site within Tsg101 is required for particle budding. In addition, mutation of a putative leucine zipper or residues important for Tsg101 multimerization also impairs the ability of Tsg101 to support HIV-1 budding. A minimal multimerizing Tsg101 domain is a dominant negative inhibitor of PTAP-mediated HIV-1 budding but does not inhibit YPDL-type or PPXY-type L-domain function. Nevertheless, YDPL-type L-domain activity is inhibited by expression of a catalytically inactive mutant of the class E VPS ATPase VPS4. These results indicate that all three classes of retroviral L domains require a functioning class E VPS pathway in order to effect budding. However, the PTAP-type L domain appears to be unique in its requirement for an intact, or nearly intact, ESCRT-I complex.
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Włoch, Wiesław, Piotr Popiel, Marek Rusin, and Anna Słowioczek. "Transformation of the domain pattern in the development of Fagus silvatica L. cambium." Acta Societatis Botanicorum Poloniae 61, no. 3-4 (2014): 331–41. http://dx.doi.org/10.5586/asbp.1992.029.
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The domain pattern of cambium during the first year of its function in <i>Fagus silvatica</i> L. resembles a checkerboard. The longitudinal line along the leaf trace, its corresponding line on the opposite side of the internode and nodes comprise the domain borders. Starting from the formation of the first annual ring, this checkerboard pattern begins to undergo gradual transformation. A transitional domain pattern appears during the first few years; in each internode, due to the alternate disappearance of Z and S domains, a fragmentary domain of one type and an expanded domain of the opposite type occur in pairs. After further transformations, a regular pattern of transverse bands of domains moving along the stem appear on older stems (over ten years-old). This pattern is commonly found in other studied species of trees.
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Abdella, Ryan, Megha Aggarwal, Takashi Okura, Robert A. Lamb, and Yuan He. "Structure of a paramyxovirus polymerase complex reveals a unique methyltransferase-CTD conformation." Proceedings of the National Academy of Sciences 117, no. 9 (February 19, 2020): 4931–41. http://dx.doi.org/10.1073/pnas.1919837117.
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Paramyxoviruses are enveloped, nonsegmented, negative-strand RNA viruses that cause a wide spectrum of human and animal diseases. The viral genome, packaged by the nucleoprotein (N), serves as a template for the polymerase complex, composed of the large protein (L) and the homo-tetrameric phosphoprotein (P). The ∼250-kDa L possesses all enzymatic activities necessary for its function but requires P in vivo. Structural information is available for individual P domains from different paramyxoviruses, but how P interacts with L and how that affects the activity of L is largely unknown due to the lack of high-resolution structures of this complex in this viral family. In this study we determined the structure of the L–P complex from parainfluenza virus 5 (PIV5) at 4.3-Å resolution using cryoelectron microscopy, as well as the oligomerization domain (OD) of P at 1.4-Å resolution using X-ray crystallography. P-OD associates with the RNA-dependent RNA polymerase domain of L and protrudes away from it, while the X domain of one chain of P is bound near the L nucleotide entry site. The methyltransferase (MTase) domain and the C-terminal domain (CTD) of L adopt a unique conformation, positioning the MTase active site immediately above the poly-ribonucleotidyltransferase domain and near the likely exit site for the product RNA 5′ end. Our study reveals a potential mechanism that mononegavirus polymerases may employ to switch between transcription and genome replication. This knowledge will assist in the design and development of antivirals against paramyxoviruses.
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Buchsbaum, R., J. B. Telliez, S. Goonesekera, and L. A. Feig. "The N-terminal pleckstrin, coiled-coil, and IQ domains of the exchange factor Ras-GRF act cooperatively to facilitate activation by calcium." Molecular and Cellular Biology 16, no. 9 (September 1996): 4888–96. http://dx.doi.org/10.1128/mcb.16.9.4888.
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We have recently shown that the neuronal exchange factor p140 Ras-GRF becomes activated in vivo in response to elevated calcium levels [C. L. Farnsworth, N. W. Freshney, L. B. Rosen, A. Ghosh, M. E. Greenberg, and L. A. Feig, Nature (London) 376:524-527, 1995]. Activation is mediated by calcium-induced calmodulin binding to an IQ domain near the N terminus of Ras-GRF. Here we show that the adjacent N-terminal pleckstrin homology (PH), coiled-coil, and IQ domains function cooperatively to allow Ras-GRF activation. Deletion of the N-terminal PH domain redistributes a large percentage of Ras-GRF from the particulate to the cytosolic fraction of cells and renders the protein insensitive to calcium stimulation. A similar cellular distribution and biological activity are observed when only the core catalytic domain is expressed. Although the PH domain is necessary for particulate association of Ras-GRF, it is not sufficient for targeting the core catalytic domain to this cellular location. This requires the PH domain and the adjacent coiled-coil and IQ sequences. Remarkably, this form of Ras-GRF is constitutively activated. The PH and coiled-coil domains must also perform an additional function, since targeting to the particulate fraction of cells is not sufficient to allow Ras-GRF activation by calcium. A Ras-GRF mutant containing the PH domain from Ras-GTPase-activating protein in place of its own N-terminal PH domain localizes to the particulate fraction of cells but does not respond to calcium. Similar phenotypes are seen with mutant Ras-GRFs containing point mutations in either the PH or coiled-coil domain. These findings argue that the N-terminal PH, coiled-coil, and IQ domains of Ras-GRF function together to connect Ras-GRF to multiple components in the particulate fractions of cells that are required for responsiveness of the protein to calcium signaling.
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Heins, S., P. C. Wong, S. Müller, K. Goldie, D. W. Cleveland, and U. Aebi. "The rod domain of NF-L determines neurofilament architecture, whereas the end domains specify filament assembly and network formation." Journal of Cell Biology 123, no. 6 (December 15, 1993): 1517–33. http://dx.doi.org/10.1083/jcb.123.6.1517.
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Neurofilaments, assembled from NF-L, NF-M, and NF-H subunits, are the most abundant structural elements in myelinated axons. Although all three subunits contain a central, alpha-helical rod domain thought to mediate filament assembly, only NF-L self-assembles into 10-nm filaments in vitro. To explore the roles of the central rod, the NH2-terminal head and the COOH-terminal tail domain in filament assembly, full-length, headless, tailless, and rod only fragments of mouse NF-L were expressed in bacteria, purified, and their structure and assembly properties examined by conventional and scanning transmission electron microscopy (TEM and STEM). These experiments revealed that in vitro assembly of NF-L into bona fide 10-nm filaments requires both end domains: whereas the NH2-terminal head domain promotes lateral association of protofilaments into protofibrils and ultimately 10-nm filaments, the COOH-terminal tail domain controls lateral assembly of protofilaments so that it terminates at the 10-nm filament level. Hence, the two end domains of NF-L have antagonistic effects on the lateral association of protofilaments into higher-order structures, with the effect of the COOH-terminal tail domain being dominant over that of the NH2-terminal head domain. Consideration of the 21-nm axial beading commonly observed with 10-nm filaments, the approximate 21-nm axial periodicity measured on paracrystals, and recent cross-linking data combine to support a molecular model for intermediate filament architecture in which the 44-46-nm long dimer rods overlap by 1-3-nm head-to-tail, whereas laterally they align antiparallel both unstaggered and approximately half-staggered.
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Kim, Joonyong, Sanghoon Kim, Sangho Lee, and Jongill Hong. "Domain wall types and field-induced domain wall motion in L-shaped nanowires." Thin Solid Films 519, no. 23 (September 2011): 8263–65. http://dx.doi.org/10.1016/j.tsf.2011.03.071.
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Frappier, T., F. Stetzkowski-Marden, and L. A. Pradel. "Interaction domains of neurofilament light chain and brain spectrin." Biochemical Journal 275, no. 2 (April 15, 1991): 521–27. http://dx.doi.org/10.1042/bj2750521.
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We have previously demonstrated that brain spectrin binds to the low-molecular-mass subunit of neurofilaments (NF-L) [Frappier, Regnouf & Pradel (1987) Eur. J. Biochem. 169, 651-657]. In the present study, we seek to locate their respective binding domains. In the first part we demonstrate that brain spectrin binds to a 20 kDa domain of NF-L. This domain is part of the rod domain of neurofilaments and plays a role in the polymerization process. However, the polymerization state does not seem to have any influence on the interaction. In the second part, we provide evidence that NF-L binds to the beta-subunit of not only brain spectrin but also human and avian erythrocyte spectrins. The microtubule-associated protein, MAP2, which has also been shown to bind to microfilaments and neurofilaments, binds to the same domain of NF-L as spectrin does. Finally, among the tryptic peptides of brain spectrin, we show that some peptides of low molecular mass (35, 25, 20 and 18 kDa) co-sediment with either NF-L or F-actin.
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Yuan, Yayan, and Jibo Li. "OnFS+-Domains." Abstract and Applied Analysis 2014 (2014): 1–4. http://dx.doi.org/10.1155/2014/850298.
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We introduce a new construction—FS+-domain—and prove that the category withFS+-domains as objects and Scott continuous functions as morphisms is a Cartesian closed category. We obtain that the Plotkin powerdomainPP(L)over anFS-domainLis anFS+-domain.
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Shehu-Xhilaga, Miranda, Sherimay Ablan, Dimiter G. Demirov, Chaoping Chen, Ronald C. Montelaro, and Eric O. Freed. "Late Domain-Dependent Inhibition of Equine Infectious Anemia Virus Budding." Journal of Virology 78, no. 2 (January 15, 2004): 724–32. http://dx.doi.org/10.1128/jvi.78.2.724-732.2004.
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ABSTRACT The Gag proteins of a number of different retroviruses contain late or L domains that promote the release of virions from the plasma membrane. Three types of L domains have been identified to date: Pro-Thr-Ala-Pro (PTAP), Pro-Pro-X-Tyr, and Tyr-Pro-Asp-Leu. It has previously been demonstrated that overexpression of the N-terminal, E2-like domain of the endosomal sorting factor TSG101 (TSG-5′) inhibits human immunodeficiency virus type 1 (HIV-1) release but does not affect the release of the PPPY-containing retrovirus murine leukemia virus (MLV), whereas overexpression of the C-terminal portion of TSG101 (TSG-3′) potently disrupts both HIV-1 and MLV budding. In addition, it has been reported that, while the release of a number of retroviruses is disrupted by proteasome inhibitors, equine infectious anemia virus (EIAV) budding is not affected by these agents. In this study, we tested the ability of TSG-5′, TSG-3′, and full-length TSG101 (TSG-F) overexpression, a dominant negative form of the AAA ATPase Vps4, and proteasome inhibitors to disrupt the budding of EIAV particles bearing each of the three types of L domain. The results indicate that (i) inhibition by TSG-5′ correlates with dependence on PTAP; (ii) the release of wild-type EIAV (EIAV/WT) is insensitive to TSG-3′, whereas this C-terminal TSG101 fragment potently impairs the budding of EIAV when it is rendered PTAP or PPPY dependent; (iii) budding of all EIAV clones is blocked by dominant negative Vps4; and (iv) EIAV/WT release is not impaired by proteasome inhibitors, while EIAV/PTAP and EIAV/PPPY release is strongly disrupted by these compounds. These findings highlight intriguing similarities and differences in host factor utilization by retroviral L domains and suggest that the insensitivity of EIAV to proteasome inhibitors is conferred by the L domain itself and not by determinants in Gag outside the L domain.
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Mattila, Polly E., Chad E. Green, Ulrich Schaff, Scott I. Simon, and Bruce Walcheck. "Cytoskeletal interactions regulate inducible L-selectin clustering." American Journal of Physiology-Cell Physiology 289, no. 2 (August 2005): C323—C332. http://dx.doi.org/10.1152/ajpcell.00603.2004.
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L-selectin (CD62L) amplifies neutrophil capture within the microvasculature at sites of inflammation. Activation by G protein-coupled stimuli or through ligation of L-selectin promotes clustering of L-selectin and serves to increase its adhesiveness, signaling, and colocalization with β2-integrins. Currently, little is known about the molecular process regulating the lateral mobility of L-selectin. On neutrophil stimulation, a progressive change takes place in the organization of its plasma membrane, resulting in membrane domains that are characteristically enriched in glycosyl phosphatidylinositol (GPI)-anchored proteins and exclude the transmembrane protein CD45. Clustering of L-selectin, facilitated by E-selectin engagement or antibody cross-linking, resulted in its colocalization with GPI-anchored CD55, but not with CD45 or CD11c. Disrupting microfilaments in neutrophils or removing a conserved cationic motif in the cytoplasmic domain of L-selectin increased its mobility and membrane domain localization in the plasma membrane. In addition, the conserved element was critical for L-selectin-dependent tethering under shear flow. Our data indicate that L-selectin’s lateral mobility is regulated by interactions with the actin cytoskeleton that in turn fortifies leukocyte tethering. We hypothesize that both membrane mobility and stabilization augment L-selectin’s effector functions and are regulated by dynamic associations with membrane domains and the actin cytoskeleton.
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Matala, Erik, Shelia R. Alexander, Takashi K. Kishimoto, and Bruce Walcheck. "The Cytoplasmic Domain of L-Selectin Participates in Regulating L-Selectin Endoproteolysis." Journal of Immunology 167, no. 3 (August 1, 2001): 1617–23. http://dx.doi.org/10.4049/jimmunol.167.3.1617.
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Miao, Vivian, Marie-Françoise Coëffet-LeGal, Paul Brian, Renee Brost, Julia Penn, Andrew Whiting, Steven Martin, et al. "Daptomycin biosynthesis in Streptomyces roseosporus: cloning and analysis of the gene cluster and revision of peptide stereochemistry." Microbiology 151, no. 5 (May 1, 2005): 1507–23. http://dx.doi.org/10.1099/mic.0.27757-0.
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Daptomycin is a 13 amino acid, cyclic lipopeptide produced by a non-ribosomal peptide synthetase (NRPS) mechanism in Streptomyces roseosporus. A 128 kb region of S. roseosporus DNA was cloned and verified by heterologous expression in Streptomyces lividans to contain the daptomycin biosynthetic gene cluster (dpt). The cloned region was completely sequenced and three genes (dptA, dptBC, dptD) encoding the three subunits of an NRPS were identified. The catalytic domains in the subunits, predicted to couple five, six or two amino acids, respectively, included a novel activation domain and amino-acid-binding pocket for incorporating the unusual amino acid l-kynurenine (Kyn), three types of condensation domains and an extra epimerase domain (E-domain) in the second module. Novel genes (dptE, dptF) whose products likely work in conjunction with a unique condensation domain to acylate the first amino acid, as well as other genes (dptI, dptJ) probably involved in supply of the non-proteinogenic amino acids l-3-methylglutamic acid and Kyn, were located next to the NRPS genes. The unexpected E-domain suggested that daptomycin would have d-Asn, rather than l-Asn, as originally assigned, and this was confirmed by comparing stereospecific synthetic peptides and the natural product both chemically and microbiologically.
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Makarov, N. N., and V. E. Semashkin. "Minimax l-optimal at Time-Domain Linear Filtering." MEHATRONIKA, AVTOMATIZACIA, UPRAVLENIE 19, no. 8 (2018): 499–507. http://dx.doi.org/10.17587/mau.19.499-507.
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Shen, Chong, and Fu-Gui Shi. "Characterizations of L-convex spaces via domain theory." Fuzzy Sets and Systems 380 (February 2020): 44–63. http://dx.doi.org/10.1016/j.fss.2019.02.009.
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Usami, Yoshiko, Sergei Popov, Elena Popova, and Heinrich G. Göttlinger. "Efficient and Specific Rescue of Human Immunodeficiency Virus Type 1 Budding Defects by a Nedd4-Like Ubiquitin Ligase." Journal of Virology 82, no. 10 (March 5, 2008): 4898–907. http://dx.doi.org/10.1128/jvi.02675-07.
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ABSTRACT To exit infected cells, human immunodeficiency virus type 1 (HIV-1) exploits the vacuolar protein-sorting pathway by engaging Tsg101 and ALIX through PTAP and LYPxnL late assembly (L) domains. In contrast, less-complex retroviruses often use PPxY L domains to recruit Nedd4 family ubiquitin ligases. Although HIV-1 Gag lacks PPxY motifs, we now show that the budding of various HIV-1 L-domain mutants is dramatically enhanced by ectopic Nedd4-2s, a native isoform with a truncated C2 domain. The effect of Nedd4-2s on HIV-1 budding required a catalytically active HECT domain and was specific, since other Nedd4 family proteins showed little activity and an unrelated retrovirus was not rescued. The residual C2 domain of Nedd4-2s was critical for the enhancement of HIV-1 budding and for the association of Nedd4-2s with Gag, as reflected by its incorporation into virus-like particles. Interestingly, the incorporation of Nedd4-2s also depended on its active site, indicating that the ability to form a thioester with ubiquitin was required. These data suggest a novel mechanism by which HIV-1 Gag can connect to cellular budding machinery.
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Usami, Yoshiko, Sergei Popov, Elena Popova, Michio Inoue, Winfried Weissenhorn, and Heinrich G. Göttlinger. "The ESCRT pathway and HIV-1 budding." Biochemical Society Transactions 37, no. 1 (January 20, 2009): 181–84. http://dx.doi.org/10.1042/bst0370181.
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HIV-1 Gag engages components of the ESCRT (endosomal sorting complex required for transport) pathway via so-called L (late-assembly) domains to promote virus budding. Specifically, the PTAP (Pro-Thr-Ala-Pro)-type primary L domain of HIV-1 recruits ESCRT-I by binding to Tsg101 (tumour susceptibility gene 101), and an auxiliary LYPXnL (Leu-Tyr-Pro-Xaan-Leu)-type L domain recruits the ESCRT-III-binding partner Alix [ALG-2 (apoptosis-linked gene 2)-interacting protein X]. The structurally related CHMPs (charged multivesicular body proteins), which form ESCRT-III, are kept in an inactive state through intramolecular interactions, and become potent inhibitors of HIV-1 budding upon removal of an autoinhibitory region. In the absence of the primary L domain, HIV-1 budding is strongly impaired, but can be efficiently rescued through the overexpression of Alix. This effect of Alix depends on its ability to interact with CHMP4, suggesting that it is the recruitment of CHMPs that ultimately drives virus release. Surprisingly, HIV-1 budding defects can also be efficiently corrected by overexpressing Nedd (neural-precursor-cell-expressed developmentally down-regulated) 4-2s, a member of a family of ubiquitin ligases previously implicated in the function of PPXY (Pro-Pro-Xaa-Tyr)-type L domains, which are absent from HIV-1. At least under certain circumstances, Nedd4-2s stimulates the activity of PTAP-type L domains, raising the possibility that the ubiquitin ligase regulates the activity of ESCRT-I.
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Kiss, I., A. H. Beaton, J. Tardiff, D. Fristrom, and J. W. Fristrom. "Interactions and developmental effects of mutations in the Broad-Complex of Drosophila melanogaster." Genetics 118, no. 2 (February 1, 1988): 247–59. http://dx.doi.org/10.1093/genetics/118.2.247.
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Abstract The 2B5 region on the X chromosome of Drosophila melanogaster forms an early ecdysone puff at the end of the third larval instar. The region contains a complex genetic locus, the Broad-Complex (BR-C) composed of four groups of fully complementing (br, rbp, l(1)2Bc, and l(1)2Bd) alleles, and classes of noncomplementing (npr 1) and partially noncomplementing l(1)2Bab alleles. BR-C mutants prevent metamorphosis, including the morphogenesis of imaginal discs. Results are presented that indicate that the BR-C contains two major functional domains. One, the br domain is primarily, if not exclusively, involved in the elongation and eversion of appendages by imaginal discs. The second, the l(1)2Bc domain, is primarily involved in the fusion of discs to form a continuous adult epidermis. Nonetheless, the two domains may encode products with related functions because in some situations mutants in both domains appear to affect similar developmental processes.
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Patton, Gillian S., Stephen A. Morris, Wayne Chung, Paul D. Bieniasz, and Myra O. McClure. "Identification of Domains in Gag Important for Prototypic Foamy Virus Egress." Journal of Virology 79, no. 10 (May 15, 2005): 6392–99. http://dx.doi.org/10.1128/jvi.79.10.6392-6399.2005.
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ABSTRACT Sequence motifs (L domains) have been described in viral structural proteins. Mutations in these lead to a defect at a late stage in virus assembly and budding. For several viruses, recruitment of an endosomal sorting complexes required for transport 1 subunit (Tsg101), a component of the class E vacuolar protein sorting (EVPS) machinery, is a prerequisite for virion budding. To effect this, Tsg101 interacts with the PT/SAP L domain. We have identified candidate L-domain motifs, PSAP, PPPI, and YEIL, in the prototypic foamy virus (PFV) Gag protein, based on their homology to known viral L domains. Mutation of the PSAP and PPPI motifs individually reduced PFV egress, and their combined mutation had an additive effect. When PSAP was mutated, residual infectious PFV release was unaffected by dominant negative Vps4 (an ATPase involved in the final stages of budding), and sensitivity to dominant negative Tsg101 was dramatically reduced, suggesting that the PSAP motif functions as a conventional class E VPS-dependent L domain. Consistent with this notion, yeast two-hybrid analysis showed a PSAP motif-dependent interaction between PFV Gag and Tsg101. Surprisingly, PFV release which is dependent on the PPPI motif was Vps4-independent and was partially inhibited by dominant negative Tsg101, suggesting that PPPI functions by an unconventional mechanism to facilitate PFV egress. Mutation of the YEIL sequence completely abolished particle formation and also reduced the rate of Gag processing by the viral protease, suggesting that the integrity of YEIL is required at an assembly step prior to budding and YEIL is not acting as an L domain.
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Monteiro, M. J., C. Hicks, L. Gu, and S. Janicki. "Determinants for intracellular sorting of cytoplasmic and nuclear intermediate filaments." Journal of Cell Biology 127, no. 5 (December 1, 1994): 1327–43. http://dx.doi.org/10.1083/jcb.127.5.1327.
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The mechanism by which nuclear and cytoplasmic filaments are sorted in vivo was studied by examining which lamin sequences are required to target an otherwise cytoplasmic IF protein, the small neurofilament subunit (NF-L), to the nuclear lamina. By swapping corresponding domains between NF-L and lamin A, nuclear envelope targeting of NF-L was shown to require the presence of the "head" domain, a 42-amino acid sequence unique to lamin rod domains, a nuclear localization signal and the CAAX motif. Replacement of the entire COOH-terminal tail of lamin A with that of NF-L had no discernible effect on nuclear localization of lamin A, provided the substituted NF-L tail contained a NLS and a CAAX motif. This chimeric protein exhibited characteristics more typical of lamin B than that of the parental lamin A. With regard to cytoplasmic assembly properties, substitution of the head domain of lamin A for that of NF-L did not substantially affect the ability of NF-L to coassemble with vimentin in the cytoplasm. In contrast, insertion of a 42-amino acid sequence unique to lamin rod domains into NF-L profoundly affected NF-L coassembly with vimentin indicating that the 42-amino acid insertion in lamins may be important for sorting lamins from cytoplasmic IF proteins.
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Kahn, J., R. H. Ingraham, F. Shirley, G. I. Migaki, and T. K. Kishimoto. "Membrane proximal cleavage of L-selectin: identification of the cleavage site and a 6-kD transmembrane peptide fragment of L-selectin." Journal of Cell Biology 125, no. 2 (April 15, 1994): 461–70. http://dx.doi.org/10.1083/jcb.125.2.461.
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Rapid downregulation of L-selectin expression occurs in response to leukocyte activation, and it has been speculated to be an integral process in the adhesion cascade leading to neutrophil recruitment to sites of inflammation. It has previously been proposed that L-selectin is proteolytically cleaved from the cell surface; however, the nature of the cleavage site has been unknown. We have produced polyclonal antisera against the extracellular domain and against the cytoplasmic domain of L-selectin. Both antisera immunoprecipitate the intact form of L-selectin from metabolically labeled phytohemagglutinin-stimulated lymphoblasts and peripheral blood neutrophils. In addition, the anti-cytoplasmic domain serum, but not the antiectodomain serum, immunoprecipitate a 6-kD species from PMA activated lymphoblasts and formylmethionylleucylphenylalanine-activated neutrophils. Conversely, the antiectodomain serum but not the anti-cytoplasmic domain serum immunoprecipitate a 68-kD soluble form of L-selectin from the supernatant of PMA-activated lymphoblasts. The appearance of the 6-kD species on activated cells correlated with the disappearance of the intact form of L-selectin and the appearance of the soluble form of L-selectin. A third polyclonal serum generated against the membrane proximal region of the ectodomain also reacted with the 6-kD species, indicating that this is a transmembrane peptide of L-selectin. That the 6-kD species is derived from L-selectin was confirmed by immunoprecipitation of the 6-kD species from L-selectin transfectants but not from mock transfectants. Radiochemical sequence analysis defined a cleavage site between Lys321 and Ser322, which would predict a transmembrane fragment consistent in size with the observed 6-kD fragment. A Ser-Phe-Ser motif adjacent to the cleavage site is conserved between human, mouse, and rat L-selectin, and a related motif is found proximal to transmembrane domains of other downregulated proteins, such as ACE, CD16-II, and TNF-RII, suggesting the possibility of a common recognition motif.
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Bindi, Luca, Leigh H. Rees, and Paola Bonazzi. "Twinning in natural melilite simulating a fivefold superstructure." Acta Crystallographica Section B Structural Science 59, no. 1 (January 28, 2003): 156–58. http://dx.doi.org/10.1107/s0108768103000041.
Full textAbstract:
Additional reflections seemingly leading to a tetragonal fivefold supercell have been observed in a number of melilites. A careful examination of the collected intensity data reveals that this feature is due to the coexistence of two twin domains related by a (1\bar20) twin plane. Reflections of the first domain (I) with h_{\rm b}^2+k_{\rm b}^2=5n overlap those of the second domain (II) when both the following additional conditions are verified: −h b + 2k b = 5n and 2h b + k b = 5n. Indices of the superimposed reflections are h b,I k b,I l b,I for the first domain, and h b,II = \textstyle{3\over5}\,h b,I + \textstyle{4\over5}\,k b,I, k b,II = \textstyle{4\over5}\,h b,I − \textstyle{3\over5}\,k b,I, l b,II = l b,I for the second domain. The non-crystallographic pseudosymmetry in the melilite structure is discussed.
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Gilmer, Robert. "On complete integral closure and Archimedean valuation domains." Journal of the Australian Mathematical Society. Series A. Pure Mathematics and Statistics 61, no. 3 (December 1996): 377–80. http://dx.doi.org/10.1017/s1446788700000458.
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AbstractSuppose D is an integral domain with quotient field K and that L is an extension field of K. We show in Theorem 4 that if the complete integral closure of D is an intersection of Archimedean valuation domains on K, then the complete integral closure of D in L is an intersection of Archimedean valuation domains on L; this answers a question raised by Gilmer and Heinzer in 1965.
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Imamura, Yuzo, Masahiko Itoh, Yoshito Maeno, Shoichiro Tsukita, and Akira Nagafuchi. "Functional Domains of α-Catenin Required for the Strong State of Cadherin-based Cell Adhesion." Journal of Cell Biology 144, no. 6 (March 22, 1999): 1311–22. http://dx.doi.org/10.1083/jcb.144.6.1311.
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The interaction of cadherin–catenin complex with the actin-based cytoskeleton through α-catenin is indispensable for cadherin-based cell adhesion activity. We reported previously that E-cadherin–α-catenin fusion molecules showed cell adhesion and cytoskeleton binding activities when expressed in nonepithelial L cells. Here, we constructed deletion mutants of E-cadherin–α-catenin fusion molecules lacking various domains of α-catenin and introduced them into L cells. Detailed analysis identified three distinct functional domains of α-catenin: a vinculin/α-actinin-binding domain, a ZO-1-binding domain, and an adhesion-modulation domain. Furthermore, cell dissociation assay revealed that the fusion molecules containing the ZO-1-binding domain in addition to the adhesion-modulation domain conferred the strong state of cell adhesion activity on transfectants, although those lacking the ZO-1-binding domain conferred only the weak state. The disorganization of actin-based cytoskeleton by cytochalasin D treatment shifted the cadherin-based cell adhesion from the strong to the weak state. In the epithelial cells, where α-catenin was not precisely colocalized with ZO-1, the ZO-1-binding domain did not completely support the strong state of cell adhesion activity. Our studies showed that the interaction of α-catenin with the actin-based cytoskeleton through the ZO-1-binding domain is required for the strong state of E-cadherin–based cell adhesion activity.
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Ruedas, J. B., and J. Perrault. "Putative Domain-Domain Interactions in the Vesicular Stomatitis Virus L Polymerase Protein Appendage Region." Journal of Virology 88, no. 24 (October 8, 2014): 14458–66. http://dx.doi.org/10.1128/jvi.02267-14.
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McCarthy, Sarah E., Reed F. Johnson, Yong-An Zhang, J. Oriol Sunyer, and Ronald N. Harty. "Role for Amino Acids 212KLR214 of Ebola Virus VP40 in Assembly and Budding." Journal of Virology 81, no. 20 (August 15, 2007): 11452–60. http://dx.doi.org/10.1128/jvi.00853-07.
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ABSTRACT Ebola virus VP40 is able to produce virus-like particles (VLPs) in the absence of other viral proteins. At least three domains within VP40 are thought to be required for efficient VLP release: the late domain (L-domain), membrane association domain (M-domain), and self-interaction domain (I-domain). While the L-domain of Ebola VP40 has been well characterized, the exact mechanism by which VP40 mediates budding through the M- and I-domains remains unclear. To identify additional domains important for VP40 assembly/budding, amino acids 212KLR214 were targeted for mutagenesis based on the published crystal structure of VP40. These residues are part of a loop connecting two beta sheets in the C-terminal region and thus are potentially important for overall structure and/or oligomerization of VP40. A series of alanine substitutions were generated in the KLR region of VP40, and these mutants were examined for VLP budding, intracellular localization, and oligomerization. Our results indicated that (i) 212KLR214 residues of VP40 are important for efficient release of VP40 VLPs, with Leu213 being the most critical; (ii) VP40 KLR mutants displayed altered patterns of cellular localization compared to that of wild-type VP40 (VP40-WT); and (iii) self-assembly of VP40 KLR mutants into oligomers was altered compared to that of VP40-WT. These results suggest that 12KLR214 residues of VP40 are important for proper assembly/oligomerization of VP40 which subsequently leads to efficient budding of VLPs.
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Dowling, Daniel P., Yan Kung, Anna K. Croft, Koli Taghizadeh, Wendy L. Kelly, Christopher T. Walsh, and Catherine L. Drennan. "Structural elements of an NRPS cyclization domain and its intermodule docking domain." Proceedings of the National Academy of Sciences 113, no. 44 (October 17, 2016): 12432–37. http://dx.doi.org/10.1073/pnas.1608615113.
Full textAbstract:
Epothilones are thiazole-containing natural products with anticancer activity that are biosynthesized by polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) enzymes EpoA–F. A cyclization domain of EpoB (Cy) assembles the thiazole functionality from an acetyl group and l-cysteine via condensation, cyclization, and dehydration. The PKS carrier protein of EpoA contributes the acetyl moiety, guided by a docking domain, whereas an NRPS EpoB carrier protein contributes l-cysteine. To visualize the structure of a cyclization domain with an accompanying docking domain, we solved a 2.03-Å resolution structure of this bidomain EpoB unit, comprising residues M1-Q497 (62 kDa) of the 160-kDa EpoB protein. We find that the N-terminal docking domain is connected to the V-shaped Cy domain by a 20-residue linker but otherwise makes no contacts to Cy. Molecular dynamic simulations and additional crystal structures reveal a high degree of flexibility for this docking domain, emphasizing the modular nature of the components of PKS-NRPS hybrid systems. These structures further reveal two 20-Å-long channels that run from distant sites on the Cy domain to the active site at the core of the enzyme, allowing two carrier proteins to dock with Cy and deliver their substrates simultaneously. Through mutagenesis and activity assays, catalytic residues N335 and D449 have been identified. Surprisingly, these residues do not map to the location of the conserved HHxxxDG motif in the structurally homologous NRPS condensation (C) domain. Thus, although both C and Cy domains have the same basic fold, their active sites appear distinct.
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Housden, N. G., S. Harrison, S. E. Roberts, J. A. Beckingham, M. Graille, E. Stura, and M. G. Gore. "Immunoglobulin-binding domains: Protein L from Peptostreptococcus magnus." Biochemical Society Transactions 31, no. 3 (June 1, 2003): 716–18. http://dx.doi.org/10.1042/bst0310716.
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Protein L is a multidomain cell-wall protein isolated from Peptostreptococcus magnus. It belongs to a group of proteins that contain repeated domains that are able to bind to Igs without stimulating an immune response, the most characterized of this group being Protein A (Staphylococcus aureus) and Protein G (Streptococcus). Both of these proteins bind predominantly to the interface of CH2-CH3 heavy chains, while Protein L binds exclusively to the VL domain of the κ-chain. The function of these proteins in vivo is not clear but it is thought that they enable the bacteria to evade the host's immune system. Two binding sites for κ-chain on a single Ig-binding domain from Protein L have recently been reported and we give evidence that one site has a 25–55-fold higher affinity for κ-chain than the second site.