3BL2
Crystal Structure of M11, the BCL-2 Homolog of Murine Gamma-herpesvirus 68, Complexed with Mouse Beclin1 (residues 106-124)
Summary for 3BL2
| Entry DOI | 10.2210/pdb3bl2/pdb |
| Descriptor | V-bcl-2, Beclin-1 (3 entities in total) |
| Functional Keywords | protein-protein complex, viral bcl-2, beclin1, apoptosis, m11, autophagy, antiviral defense, coiled coil, cytoplasm, golgi apparatus, membrane, viral protein-apoptosis complex, viral protein/apoptosis |
| Biological source | Murid herpesvirus 4 (Murine herpesvirus 68) More |
| Cellular location | Cytoplasm . Beclin-1-C 35 kDa: Mitochondrion . Beclin-1-C 37 kDa: Mitochondrion : O88597 |
| Total number of polymer chains | 4 |
| Total formula weight | 34789.75 |
| Authors | Oh, B.-H.,Woo, J.-S.,Ku, B. (deposition date: 2007-12-10, release date: 2008-02-12, Last modification date: 2023-11-01) |
| Primary citation | Ku, B.,Woo, J.-S.,Liang, C.,Lee, K.-H.,Hong, H.-S.,E, X.,Kim, K.-S.,Jung, J.U.,Oh, B.-H. Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine gamma-Herpesvirus 68 Plos Pathog., 4:e25-e25, 2008 Cited by PubMed Abstract: 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. PubMed: 18248095DOI: 10.1371/journal.ppat.0040025 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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