5wos
From Proteopedia
Structural and functional insights into Canarypox Virus CNP058 regulation of apoptosis
Structural highlights
FunctionARBH_CNPV Plays a role in the inhibition of host apoptosis. Interacts with host proapoptotic factors BAK1 and BAX to supposedly prevent their activation.[1] Publication Abstract from PubMedProgrammed cell death or apoptosis is an important component of host defense systems against viral infection. The B-cell lymphoma 2 (Bcl-2) proteins family is the main arbiter of mitochondrially mediated apoptosis, and viruses have evolved sequence and structural mimics of Bcl-2 to subvert premature host cell apoptosis in response to viral infection. The sequencing of the canarypox virus genome identified a putative pro-survival Bcl-2 protein, CNP058. However, a role in apoptosis inhibition for CNP058 has not been identified to date. Here, we report that CNP058 is able to bind several host cell pro-death Bcl-2 proteins, including Bak and Bax, as well as several BH3 only-proteins including Bim, Bid, Bmf, Noxa, Puma, and Hrk with high to moderate affinities. We then defined the structural basis for CNP058 binding to pro-death Bcl-2 proteins by determining the crystal structure of CNP058 bound to Bim BH3. CNP058 adopts the conserved Bcl-2 like fold observed in cellular pro-survival Bcl-2 proteins, and utilizes the canonical ligand binding groove to bind Bim BH3. We then demonstrate that CNP058 is a potent inhibitor of ultraviolet (UV) induced apoptosis in a cell culture model. Our findings suggest that CNP058 is a potent inhibitor of apoptosis that is able to bind to BH3 domain peptides from a broad range of pro-death Bcl-2 proteins, and may play a key role in countering premature host apoptosis. Structural and Functional Insight into Canarypox Virus CNP058 Mediated Regulation of Apoptosis.,Anasir MI, Baxter AA, Poon IKH, Hulett MD, Kvansakul M Viruses. 2017 Oct 20;9(10). pii: E305. doi: 10.3390/v9100305. PMID:29053589[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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