|
|
| Line 1: |
Line 1: |
| | | | |
| | ==The structure of the Trim5alpha Bbox- coiled coil in complex LC3B== | | ==The structure of the Trim5alpha Bbox- coiled coil in complex LC3B== |
| - | <StructureSection load='5w9a' size='340' side='right' caption='[[5w9a]], [[Resolution|resolution]] 2.74Å' scene=''> | + | <StructureSection load='5w9a' size='340' side='right'caption='[[5w9a]], [[Resolution|resolution]] 2.74Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w9a]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Macmu Macmu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W9A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W9A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w9a]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W9A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W9A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.74Å</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]), MAP1LC3B, MAP1ALC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </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=5w9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w9a OCA], [https://pdbe.org/5w9a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w9a RCSB], [https://www.ebi.ac.uk/pdbsum/5w9a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w9a ProSAT]</span></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=5w9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w9a OCA], [http://pdbe.org/5w9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w9a RCSB], [http://www.ebi.ac.uk/pdbsum/5w9a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w9a 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> [[http://www.uniprot.org/uniprot/MLP3B_HUMAN MLP3B_HUMAN]] Involved in formation of autophagosomal vacuoles (autophagosomes). | + | [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 == |
| Line 20: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 5w9a" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5w9a" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Microtubule-associated protein 3D structures|Microtubule-associated protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Macmu]] | + | [[Category: Large Structures]] |
| - | [[Category: RING-type E3 ubiquitin transferase]] | + | [[Category: Macaca mulatta]] |
| - | [[Category: Goldstone, D C]] | + | [[Category: Goldstone DC]] |
| - | [[Category: Keown, J R]] | + | [[Category: Keown JR]] |
| - | [[Category: Antiviral protein]]
| + | |
| - | [[Category: Autophagy trim5alpha lc3b antiviral protein]]
| + | |
| 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
The retroviral restriction factor Trim5alpha acts during the early post entry stages of the retroviral life cycle to block infection by a broad range of retroviruses, disrupting reverse transcription and integration. The mechanism of this restriction is poorly understood but it has recently been suggested to involve recruitment of components of the autophagy machinery, including members of the mammalian autophagy related 8 (ATG8) family involved in targeting proteins to the autophagosome. To better understand the molecular details of this interaction, here we utilized analytical ultracentrifugation to characterize the binding of six ATG8 isoforms and determined the crystal structure of the Trim5alpha Bbox-coiled-coil region in complex with one member of the mammalian ATG8 proteins, autophagy-related protein LC3B (LC3B). We found that Trim5alpha binds all mammalian ATG8s and unlike the typical LC3-interacting region (LIR) that binds to mammalian ATG8s through a beta-strand motif comprising approximately six residues, we find that LC3B binds to Trim5alpha via the a-helical coiled-coil region. The orientation of the structure demonstrates that LC3B could be accommodated within a Trim5alpha assembly that can bind the retroviral capsid. However, mutation of the binding interface does not effect retroviral restriction. Comparison of the typical linear beta-strand LIR with our atypical helical LIR reveals a conservation of the presentation of residues that are required for the interaction with LC3B. This observation expands the range of LC3B binding proteins to include helical binding motifs and demonstrates a link between Trim5alpha and components of the autophagosome.
A helical LIR mediates the interaction between the retroviral restriction factor Trim5alpha and the mammalian autophagy related ATG8 proteins.,Keown JR, Black MM, Ferron A, Yap MW, Barnett MJ, Pearce FG, Stoye JP, Goldstone DC J Biol Chem. 2018 Oct 3. pii: RA118.004202. doi: 10.1074/jbc.RA118.004202. PMID:30282803[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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, Black MM, Ferron A, Yap MW, Barnett MJ, Pearce FG, Stoye JP, Goldstone DC. A helical LIR mediates the interaction between the retroviral restriction factor Trim5alpha and the mammalian autophagy related ATG8 proteins. J Biol Chem. 2018 Oct 3. pii: RA118.004202. doi: 10.1074/jbc.RA118.004202. PMID:30282803 doi:http://dx.doi.org/10.1074/jbc.RA118.004202
|
