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| | ==Crystal structure of the complex of murine gamma-herpesvirus 68 Bcl-2 homolog M11 and the Beclin 1 BH3 domain== | | ==Crystal structure of the complex of murine gamma-herpesvirus 68 Bcl-2 homolog M11 and the Beclin 1 BH3 domain== |
| - | <StructureSection load='3dvu' size='340' side='right' caption='[[3dvu]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='3dvu' size='340' side='right'caption='[[3dvu]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dvu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mhv68 Mhv68]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DVU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dvu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Murid_gammaherpesvirus_4 Murid gammaherpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DVU FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bl2|3bl2]]</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]] 2.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">v-bcl-2, GAMMAHV.M11, M11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=33708 MHV68])</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=3dvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dvu OCA], [https://pdbe.org/3dvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dvu RCSB], [https://www.ebi.ac.uk/pdbsum/3dvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dvu 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=3dvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dvu OCA], [http://pdbe.org/3dvu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dvu RCSB], [http://www.ebi.ac.uk/pdbsum/3dvu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dvu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BECN1_HUMAN BECN1_HUMAN]] Plays a central role in autophagy. Required for the abcission step in cytokinesis. May play a role in antiviral host defense. Protects against infection by a neurovirulent strain of Sindbis virus.<ref>PMID:20208530</ref> | + | [https://www.uniprot.org/uniprot/ARBH_MHV68 ARBH_MHV68] Plays a role in the protection against apoptosis mediated by cytotoxic cells during the immune response to acute and persistent viral infection. Contributes therefore to latency establishment. Plays also a role in the inhibition of host starvation-induced autophagy which ultimately contributes to the viral chronic infection.<ref>PMID:10573168</ref> <ref>PMID:11205127</ref> <ref>PMID:15604429</ref> <ref>PMID:18248095</ref> <ref>PMID:18797192</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3dvu" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3dvu" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Mhv68]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Sinha, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Antiviral defense]] | + | [[Category: Murid gammaherpesvirus 4]] |
| - | [[Category: Apoptosis]] | + | [[Category: Sinha S]] |
| - | [[Category: Autophagy]]
| + | |
| - | [[Category: Beclin 1]]
| + | |
| - | [[Category: Bh3 domain]]
| + | |
| - | [[Category: Coiled coil]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Golgi apparatus]]
| + | |
| - | [[Category: M11]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Protein-protein complex]]
| + | |
| - | [[Category: Viral bcl-2]]
| + | |
| - | [[Category: Viral protein-apoptosis complex]]
| + | |
| Structural highlights
Function
ARBH_MHV68 Plays a role in the protection against apoptosis mediated by cytotoxic cells during the immune response to acute and persistent viral infection. Contributes therefore to latency establishment. Plays also a role in the inhibition of host starvation-induced autophagy which ultimately contributes to the viral chronic infection.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
gamma-Herpesviruses (gammaHVs), including important human pathogens such as Epstein Barr virus, Kaposi's sarcoma-associated HV, and the murine gammaHV68, encode homologs of the antiapoptotic, cellular Bcl-2 (cBcl-2) to promote viral replication and pathogenesis. The precise molecular details by which these proteins function in viral infection are poorly understood. Autophagy, a lysosomal degradation pathway, is inhibited by the interaction of cBcl-2s with a key autophagy effector, Beclin 1, and can also be inhibited by gammaHV Bcl-2s. Here we investigate the gammaHV68 M11-Beclin 1 interaction in atomic detail, using biochemical and structural approaches. We show that the Beclin 1 BH3 domain is the primary determinant of binding to M11 and other Bcl-2s, and this domain binds in a hydrophobic groove on M11, reminiscent of the binding of different BH3 domains to other Bcl-2s. Unexpectedly, regions outside of, but contiguous with, the Beclin 1 BH3 domain also contribute to this interaction. We find that M11 binds to Beclin 1 more strongly than do KSHV Bcl-2 or cBcl-2. Further, the differential affinity of M11 for different BH3 domains is caused by subtle, yet significant, variations in the atomic details of each interaction. Consistent with our structural analysis, we find that Beclin 1 residues L116 and F123, and M11 residue pairs G86 + R87 and Y60 + L74, are required for M11 to bind to Beclin 1 and downregulate autophagy. Thus, our results suggest that M11 inhibits autophagy through a mechanism that involves the binding of the Beclin 1 BH3 domain in the M11 hydrophobic surface groove.
Molecular basis of the regulation of Beclin 1-dependent autophagy by the gamma-herpesvirus 68 Bcl-2 homolog M11.,Sinha S, Colbert CL, Becker N, Wei Y, Levine B Autophagy. 2008 Nov 18;4(8). PMID:18797192[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang GH, Garvey TL, Cohen JI. The murine gammaherpesvirus-68 M11 protein inhibits Fas- and TNF-induced apoptosis. J Gen Virol. 1999 Oct;80 ( Pt 10):2737-2740. doi: 10.1099/0022-1317-80-10-2737. PMID:10573168 doi:http://dx.doi.org/10.1099/0022-1317-80-10-2737
- ↑ Roy DJ, Ebrahimi BC, Dutia BM, Nash AA, Stewart JP. Murine gammaherpesvirus M11 gene product inhibits apoptosis and is expressed during virus persistence. Arch Virol. 2000;145(11):2411-20. doi: 10.1007/s007050070030. PMID:11205127 doi:http://dx.doi.org/10.1007/s007050070030
- ↑ de Lima BD, May JS, Marques S, Simas JP, Stevenson PG. Murine gammaherpesvirus 68 bcl-2 homologue contributes to latency establishment in vivo. J Gen Virol. 2005 Jan;86(Pt 1):31-40. doi: 10.1099/vir.0.80480-0. PMID:15604429 doi:http://dx.doi.org/10.1099/vir.0.80480-0
- ↑ Ku B, Woo JS, Liang C, Lee KH, Hong HS, E X, Kim KS, Jung JU, Oh BH. Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine gamma-Herpesvirus 68. PLoS Pathog. 2008 Feb 1;4(2):e25. PMID:18248095 doi:07-PLPA-RA-0558
- ↑ Sinha S, Colbert CL, Becker N, Wei Y, Levine B. Molecular basis of the regulation of Beclin 1-dependent autophagy by the gamma-herpesvirus 68 Bcl-2 homolog M11. Autophagy. 2008 Nov 18;4(8). PMID:18797192
- ↑ Sinha S, Colbert CL, Becker N, Wei Y, Levine B. Molecular basis of the regulation of Beclin 1-dependent autophagy by the gamma-herpesvirus 68 Bcl-2 homolog M11. Autophagy. 2008 Nov 18;4(8). PMID:18797192
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