5tzp

Crystal structure of FPV039:Bik BH3 complex

spinqualitylabelsall models 5tzp, resolution 1.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5tzp is a 2 chain structure with sequence from Fowlpox virus strain NVSL and Gallus gallus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.35Å Ligands: EDO, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ARBH_FOWPN Plays a role in the inhibition of host apoptosis by sequestering and inactivating multiple proapoptotic BCL-2 proteins, including BAK1 and BAX. Publication Abstract from PubMed Programmed cell death or apoptosis of infected host cells is an important defense mechanism in response to viral infections. This process is regulated by pro-apoptotic and pro-survival members of the B-cell lymphoma 2 (Bcl-2) protein family. To counter premature death of a virus-infected cell, poxviruses use a range of different molecular strategies, including the mimicry of pro-survival Bcl-2 proteins. One such viral pro-survival protein is the fowlpox virus protein FPV039, which is a potent apoptosis inhibitor, but the precise molecular mechanism by which FPV039 inhibits apoptosis is unknown. To understand how fowlpox virus inhibits apoptosis we examined FPV039 using isothermal titration calorimetry, small-angle X-ray scattering and X-ray crystallography. Here, we report that the fowlpox virus pro-survival protein FPV039 promiscuously binds to cellular pro-apoptotic Bcl-2, and engages all major pro-apoptotic Bcl-2 proteins. Unlike other identified viral Bcl-2 proteins to date, FPV039 engaged with cellular pro-apoptotic Bcl-2 with affinities comparable to those of Bcl-2's endogenous cellular counterparts. Structural studies revealed that FPV039 adopts the conserved Bcl-2 fold observed in cellular pro-survival Bcl-2 proteins, and closely mimics the structure of the pro-survival Bcl-2 family protein Mcl-1. Our findings suggest that FPV039 is a pan Bcl-2 protein inhibitor that can engage all host BH3-only proteins as well as Bcl-2 associated X, apoptosis regulator (Bax) and Bcl-2 antagonist/killer (Bak) proteins to inhibit premature apoptosis of an infected host cell. This work therefore provides a mechanistic platform to better understand FPV039-mediated apoptosis inhibition. Structural Basis of Apoptosis Inhibition by the Fowlpox Virus Protein FPV039.,Anasir MI, Caria S, Skinner MA, Kvansakul M J Biol Chem. 2017 Apr 14. pii: jbc.M116.768879. doi: 10.1074/jbc.M116.768879. PMID:28411240 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also B-cell lymphoma proteins 3D structures

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