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| | ==NMR structure of gamma herpesvirus 68 a viral Bcl-2 homolog== | | ==NMR structure of gamma herpesvirus 68 a viral Bcl-2 homolog== |
| - | <StructureSection load='2abo' size='340' side='right'caption='[[2abo]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='2abo' size='340' side='right'caption='[[2abo]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2abo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mhv68 Mhv68]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ABO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ABO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2abo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Murid_gammaherpesvirus_4 Murid gammaherpesvirus 4]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ABO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ABO FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gamma HV68 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=33708 MHV68])</td></tr> | + | </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=2abo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2abo OCA], [https://pdbe.org/2abo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2abo RCSB], [https://www.ebi.ac.uk/pdbsum/2abo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2abo 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=2abo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2abo OCA], [https://pdbe.org/2abo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2abo RCSB], [https://www.ebi.ac.uk/pdbsum/2abo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2abo ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [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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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mhv68]] | + | [[Category: Murid gammaherpesvirus 4]] |
| - | [[Category: Dyk, L F.van]]
| + | [[Category: Huang Q]] |
| - | [[Category: Huang, Q]] | + | [[Category: Labrada L]] |
| - | [[Category: Labrada, L]] | + | [[Category: Levine B]] |
| - | [[Category: Levine, B]] | + | [[Category: Loh J]] |
| - | [[Category: Loh, J]] | + | [[Category: Nettesheim D]] |
| - | [[Category: Nettesheim, D]] | + | [[Category: Olejniczak ET]] |
| - | [[Category: Olejniczak, E T]] | + | [[Category: Petros AM]] |
| - | [[Category: Petros, A M]] | + | [[Category: Speck SH]] |
| - | [[Category: Speck, S H]] | + | [[Category: Virgin HW]] |
| - | [[Category: Virgin, H W]] | + | [[Category: Van Dyk LF]] |
| - | [[Category: Murine gamma herpes virus]] | + | |
| - | [[Category: Viral bcl-2 homolog]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| 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
Antiapoptotic Bcl-2 family proteins inhibit apoptosis in cultured cells by binding BH3 domains of proapoptotic Bcl-2 family members via a hydrophobic BH3 binding groove on the protein surface. We investigated the physiological importance of the BH3 binding groove of an antiapoptotic Bcl-2 protein in mammals in vivo by analyzing a viral Bcl-2 family protein. We show that the gamma-herpesvirus 68 (gammaHV68) Bcl-2 family protein (gammaHV68 v-Bcl-2), which is known to inhibit apoptosis in cultured cells, inhibits both apoptosis in primary lymphocytes and Bax toxicity in yeast. Nuclear magnetic resonance determination of the gammaHV68 v-Bcl-2 structure revealed a BH3 binding groove that binds BH3 domain peptides from proapoptotic Bcl-2 family members Bax and Bak via a molecular mechanism shared with host Bcl-2 family proteins, involving a conserved arginine in the BH3 peptide binding groove. Mutations of this conserved arginine and two adjacent amino acids to alanine (SGR to AAA) within the BH3 binding groove resulted in a properly folded protein that lacked the capacity of the wild-type gammaHV68 v-Bcl-2 to bind Bax BH3 peptide and to block Bax toxicity in yeast. We tested the physiological importance of this v-Bcl-2 domain during viral infection by engineering viral mutants encoding a v-Bcl-2 containing the SGR to AAA mutation. This mutation resulted in a virus defective for both efficient reactivation of gammaHV68 from latency and efficient persistent gammaHV68 replication. These studies demonstrate an essential functional role for amino acids in the BH3 peptide binding groove of a viral Bcl-2 family member during chronic infection.
A surface groove essential for viral Bcl-2 function during chronic infection in vivo.,Loh J, Huang Q, Petros AM, Nettesheim D, van Dyk LF, Labrada L, Speck SH, Levine B, Olejniczak ET, Virgin HW 4th PLoS Pathog. 2005 Sep;1(1):e10. Epub 2005 Sep 30. PMID:16201011[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Loh J, Huang Q, Petros AM, Nettesheim D, van Dyk LF, Labrada L, Speck SH, Levine B, Olejniczak ET, Virgin HW 4th. A surface groove essential for viral Bcl-2 function during chronic infection in vivo. PLoS Pathog. 2005 Sep;1(1):e10. Epub 2005 Sep 30. PMID:16201011 doi:http://dx.doi.org/10.1371/journal.ppat.0010010
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