2xpx

Crystal structure of BHRF1:Bak BH3 complex

spinqualitylabelsall models 2xpx, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xpx is a 2 chain structure with sequence from Homo sapiens and Human herpesvirus 4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, NO3 Related: 1bxl, 2jcn, 2jby, 1q59 Resources: FirstGlance, OCA, RCSB, PDBsum Function [EAR_EBVB9] Prevents premature death of the host cell during virus production, which would otherwise reduce the amount of progeny virus. Acts as a host B-cell leukemia/lymphoma 2 (Bcl-2) homolog, and interacts with pro-apoptotic proteins to prevent mitochondria permeabilization, release of cytochrome c and subsequent apoptosis of the host cell. [BAK_HUMAN] In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis. Publication Abstract from PubMed Epstein-Barr virus (EBV) is associated with human malignancies, especially those affecting the B cell compartment such as Burkitt lymphoma. The virally encoded homolog of the mammalian pro-survival protein Bcl-2, BHRF1 contributes to viral infectivity and lymphomagenesis. In addition to the pro-apoptotic BH3-only protein Bim, its key target in lymphoid cells, BHRF1 also binds a selective sub-set of pro-apoptotic proteins (Bid, Puma, Bak) expressed by host cells. A consequence of BHRF1 expression is marked resistance to a range of cytotoxic agents and in particular, we show that its expression renders a mouse model of Burkitt lymphoma untreatable. As current small organic antagonists of Bcl-2 do not target BHRF1, the structures of it in complex with Bim or Bak shown here will be useful to guide efforts to target BHRF1 in EBV-associated malignancies, which are usually associated with poor clinical outcomes. Structural Basis for Apoptosis Inhibition by Epstein-Barr Virus BHRF1.,Kvansakul M, Wei AH, Fletcher JI, Willis SN, Chen L, Roberts AW, Huang DC, Colman PM PLoS Pathog. 2010 Dec 23;6(12):e1001236. PMID:21203485 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Bcl-2

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