| 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
All gammaherpesviruses express homologues of antiapoptotic B-cell lymphoma-2 (BCL-2) to counter the clearance of infected cells by host antiviral defense machineries. To gain insights into the action mechanisms of these viral BCL-2 proteins, we carried out structural and biochemical analyses on the interactions of M11, a viral BCL-2 of murine gamma-herpesvirus 68, with a fragment of proautophagic Beclin1 and BCL-2 homology 3 (BH3) domain-containing peptides derived from an array of proapoptotic BCL-2 family proteins. Mainly through hydrophobic interactions, M11 bound the BH3-like domain of Beclin1 with a dissociation constant of 40 nanomole, a markedly tighter affinity compared to the 1.7 micromolar binding affinity between cellular BCL-2 and Beclin1. Consistently, M11 inhibited autophagy more efficiently than BCL-2 in NIH3T3 cells. M11 also interacted tightly with a BH3 domain peptide of BAK and those of the upstream BH3-only proteins BIM, BID, BMF, PUMA, and Noxa, but weakly with that of BAX. These results collectively suggest that M11 potently inhibits Beclin1 in addition to broadly neutralizing the proapoptotic BCL-2 family in a similar but distinctive way from cellular BCL-2, and that the Beclin1-mediated autophagy may be a main target of the virus.
Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine gamma-Herpesvirus 68.,Ku B, Woo JS, Liang C, Lee KH, Hong HS, E X, Kim KS, Jung JU, Oh BH PLoS Pathog. 2008 Feb 1;4(2):e25. PMID:18248095[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
- ↑ 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
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