2lm3: Difference between revisions
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==Structure of the rhesus monkey TRIM5alpha PRYSPRY domain== | ==Structure of the rhesus monkey TRIM5alpha PRYSPRY domain== | ||
<StructureSection load='2lm3' size='340' side='right'caption='[[2lm3 | <StructureSection load='2lm3' size='340' side='right'caption='[[2lm3]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2lm3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2lm3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta Macaca mulatta]. The July 2013 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''HIV Capsid'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2013_7 10.2210/rcsb_pdb/mom_2013_7]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LM3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LM3 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lm3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lm3 OCA], [https://pdbe.org/2lm3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lm3 RCSB], [https://www.ebi.ac.uk/pdbsum/2lm3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lm3 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lm3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lm3 OCA], [https://pdbe.org/2lm3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lm3 RCSB], [https://www.ebi.ac.uk/pdbsum/2lm3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lm3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/TRIM5_MACMU TRIM5_MACMU] Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. Blocks viral replication early in the life cycle, after viral entry but before reverse transcription. In addition to acting as a capsid-specific restriction factor, also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Binding to the viral capsid triggers its E3 ubiquitin ligase activity, and in concert with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-UBE2N (also known as UBC13-UEV1A complex) generates 'Lys-63'-linked polyubiquitin chains, which in turn are catalysts in the autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2, and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes, thereby leading to an innate immune response in the infected cell. Restricts infection by human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV-agm).<ref>PMID:21734049</ref> <ref>PMID:21035162</ref> <ref>PMID:22291694</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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[[Category: HIV Capsid]] | [[Category: HIV Capsid]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Macaca mulatta]] | ||
[[Category: RCSB PDB Molecule of the Month]] | [[Category: RCSB PDB Molecule of the Month]] | ||
[[Category: Biris | [[Category: Biris N]] | ||
[[Category: Diaz-Griffero | [[Category: Diaz-Griffero F]] | ||
[[Category: Guo | [[Category: Guo M]] | ||
[[Category: Hart | [[Category: Hart PJ]] | ||
[[Category: Ivanov | [[Category: Ivanov DN]] | ||
[[Category: Taylor | [[Category: Taylor AB]] | ||
[[Category: Tomashevski | [[Category: Tomashevski A]] | ||
[[Category: Yang | [[Category: Yang Y]] | ||
Latest revision as of 08:46, 15 May 2024
Structure of the rhesus monkey TRIM5alpha PRYSPRY domainStructure of the rhesus monkey TRIM5alpha PRYSPRY domain
Structural highlights
FunctionTRIM5_MACMU Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. Blocks viral replication early in the life cycle, after viral entry but before reverse transcription. In addition to acting as a capsid-specific restriction factor, also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Binding to the viral capsid triggers its E3 ubiquitin ligase activity, and in concert with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-UBE2N (also known as UBC13-UEV1A complex) generates 'Lys-63'-linked polyubiquitin chains, which in turn are catalysts in the autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2, and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes, thereby leading to an innate immune response in the infected cell. Restricts infection by human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV-agm).[1] [2] [3] Publication Abstract from PubMedTripartite motif protein TRIM5alpha blocks retroviral replication after cell entry, and species-specific differences in its activity are determined by sequence variations within the C-terminal B30.2/PRYSPRY domain. Here we report a high-resolution structure of a TRIM5alpha PRYSPRY domain, the PRYSPRY of the rhesus monkey TRIM5alpha that potently restricts HIV infection, and identify features involved in its interaction with the HIV capsid. The extensive capsid-binding interface maps on the structurally divergent face of the protein formed by hypervariable loop segments, confirming that TRIM5alpha evolution is largely determined by its binding specificity. Interactions with the capsid are mediated by flexible variable loops via a mechanism that parallels antigen recognition by IgM antibodies, a similarity that may help explain some of the unusual functional properties of TRIM5alpha. Distinctive features of this pathogen-recognition interface, such as structural plasticity conferred by the mobile v1 segment and interaction with multiple epitopes, may allow restriction of divergent retroviruses and increase resistance to capsid mutations. Structure of the rhesus monkey TRIM5alpha PRYSPRY domain, the HIV capsid recognition module.,Biris N, Yang Y, Taylor AB, Tomashevski A, Guo M, Hart PJ, Diaz-Griffero F, Ivanov DN Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13278-83. doi:, 10.1073/pnas.1203536109. Epub 2012 Jul 30. PMID:22847415[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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