2wh6

Crystal structure of anti-apoptotic BHRF1 in complex with the Bim BH3 domain

spinqualitylabelsall models 2wh6, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wh6 is a 2 chain structure with sequence from Epstein-barr virus strain ag876 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: BR, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function EAR_EBVA8 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 (By similarity). 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.

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