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| | ==Rhesus macaques Trim5alpha Bbox2 domain== | | ==Rhesus macaques Trim5alpha Bbox2 domain== |
| - | <StructureSection load='5k3q' size='340' side='right' caption='[[5k3q]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='5k3q' size='340' side='right'caption='[[5k3q]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5k3q]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Macmu Macmu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K3Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K3Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5k3q]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K3Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K3Q FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRIM5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9544 MACMU])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5k3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k3q OCA], [http://pdbe.org/5k3q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k3q RCSB], [http://www.ebi.ac.uk/pdbsum/5k3q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k3q 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=5k3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k3q OCA], [https://pdbe.org/5k3q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k3q RCSB], [https://www.ebi.ac.uk/pdbsum/5k3q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k3q ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Macmu]] | + | [[Category: Large Structures]] |
| - | [[Category: Goldstone, D C]] | + | [[Category: Macaca mulatta]] |
| - | [[Category: Keown, J K]] | + | [[Category: Goldstone DC]] |
| - | [[Category: Ligase]] | + | [[Category: Keown JK]] |
| - | [[Category: Zinc finger bbox2 antiretroviral]]
| + | |
| Structural highlights
Function
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).[1] [2] [3]
Publication Abstract from PubMed
Retroviral pathogens have been an evolutionary pressure for many primate species, driving the development of an intrinsic cellular response to retroviruses and antiretroviral proteins. One such antiretroviral protein is the restriction factor Trim5alpha, that blocks HIV-1 infection in rhesus macaques at an early post-entry stage in the retroviral lifecycle. Trim5alpha self-assembles into a large hexagonal array, complimentary to the retroviral capsid. Assembly is mediated by the conserved N-terminal architecture comprising a RING domain, a Bbox domain, and a coiled coil. Recently we have shown that the Bbox domain and elements of the coiled coil form a trimer in solution, and that the Bbox domain drives assembly. During crystallisation experiments using the trimer forming construct, we determined the structure of a dimeric Bbox domain to a resolution of 1.8A. Interface analysis reveals that residues previously shown to be required for assembly and restriction, Glu120 and Arg121, are central to the interface. Comparison to a mutant Trim5alpha dimer interface shows a translation of the Bbox dimerisation interface removing interactions important in the wildtype protein.
Crystal structure of the Trim5alpha Bbox2 domain from rhesus macaques describes a plastic oligomerisation interface.,Keown JR, Goldstone DC J Struct Biol. 2016 Jul 9. pii: S1047-8477(16)30145-9. doi:, 10.1016/j.jsb.2016.07.004. PMID:27402535[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lienlaf M, Hayashi F, Di Nunzio F, Tochio N, Kigawa T, Yokoyama S, Diaz-Griffero F. Contribution of E3-ubiquitin ligase activity to HIV-1 restriction by TRIM5alpha(rh): structure of the RING domain of TRIM5alpha. J Virol. 2011 Sep;85(17):8725-37. Epub 2011 Jul 6. PMID:21734049 doi:10.1128/JVI.00497-11
- ↑ Tareen SU, Emerman M. Human Trim5alpha has additional activities that are uncoupled from retroviral capsid recognition. Virology. 2011 Jan 5;409(1):113-20. doi: 10.1016/j.virol.2010.09.018. Epub 2010, Oct 28. PMID:21035162 doi:10.1016/j.virol.2010.09.018
- ↑ Nakayama EE, Shioda T. TRIM5alpha and Species Tropism of HIV/SIV. Front Microbiol. 2012;3:13. doi: 10.3389/fmicb.2012.00013. Epub 2012 Jan 24. PMID:22291694 doi:10.3389/fmicb.2012.00013
- ↑ Keown JR, Goldstone DC. Crystal structure of the Trim5alpha Bbox2 domain from rhesus macaques describes a plastic oligomerisation interface. J Struct Biol. 2016 Jul 9. pii: S1047-8477(16)30145-9. doi:, 10.1016/j.jsb.2016.07.004. PMID:27402535 doi:http://dx.doi.org/10.1016/j.jsb.2016.07.004
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