Cell death or apoptosis is a key feature utilized by multicellular organisms as immune response. In particular, propagation of viruses using host cells can be prevented by such a mechanism. Consequently certain viruses developed different tools to avoid host apoptosis. Amongst them, large DNA viruses such as the poxviruses code for apoptotic receptor decoys or expresses anti-apoptotic Bcl-2 protein.
Deerpox is a member of the Cervipox, and expresses a putative viral Bcl-2 protein, DPV022. Despite the lack of obvious sequence homology with cellular and viral Bcl-2, DPV022 has been shown to interact with Bak and Bax, the executioner of mitochondrial membrane permeabilization.
In this on-going project, we assessed the affinity of DPV022 with cellular Bcl-2, and based on the outcomes created a complex of DPV022 with a Bim peptide. Following crystallization of the complex we determined the 3D structure of DPV022-Bim by X-ray crystallography. Not only does the structure confirm the Bcl-2 fold, but it surprisingly shows the dimerization by domain swapping that is only observe in one other Bcl-2 molecule, vaccinia virus F1L. This study allows us to acquire a better understanding on viral subversion of the host apoptosis, but also better understand why they are less subject to regulation than cellular Bcl-2.