5tzp
From Proteopedia
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ARBH_FOWPN ARBH_FOWPN] Plays a role in the inhibition of host apoptosis by sequestering and inactivating multiple proapoptotic BCL-2 proteins, including BAK1 and BAX.<ref>PMID:19439472</ref> | [https://www.uniprot.org/uniprot/ARBH_FOWPN ARBH_FOWPN] Plays a role in the inhibition of host apoptosis by sequestering and inactivating multiple proapoptotic BCL-2 proteins, including BAK1 and BAX.<ref>PMID:19439472</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
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| + | 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<ref>PMID:28411240</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5tzp" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Crystal structure of FPV039:Bik BH3 complex
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