| Structural highlights
Function
[BECN1_MOUSE] Plays a central role in autophagy. Required for the abcission step in cytokinesis. May play a role in antiviral host defense.[1] [2] [3]
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999 Dec 9;402(6762):672-6. PMID:10604474 doi:http://dx.doi.org/10.1038/45257
- ↑ Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N. A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice. Neuron. 2002 Aug 29;35(5):921-33. PMID:12372286
- ↑ Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, Heintz N, Yue Z. Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol. 2009 Apr;11(4):468-76. doi: 10.1038/ncb1854. Epub 2009 Mar 8. PMID:19270693 doi:http://dx.doi.org/10.1038/ncb1854
- ↑ 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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