Journal article
Vaccinia virus anti-apoptotic F1L is a novel Bcl-2-like domain-swapped dimer that binds a highly selective subset of BH3-containing death ligands
M Kvansakul, H Yang, WD Fairlie, PE Czabotar, SF Fischer, MA Perugini, DCS Huang, PM Colman
Cell Death and Differentiation | NATURE PUBLISHING GROUP | Published : 2008
DOI: 10.1038/cdd.2008.83
Abstract
Apoptosis is an important part of the host's defense mechanism for eliminating invading pathogens. Some viruses express proteins homologous in sequence and function to mammalian pro-survival Bcl-2 proteins. Anti-apoptotic F1L expressed by vaccinia virus is essential for survival of infected cells, but it bears no discernable sequence homology to proteins other than its immediate orthologues in related pox viruses. Here we report that the crystal structure of F1L reveals a Bcl-2-like fold with an unusual N-terminal extension. The protein forms a novel domain-swapped dimer in which the α1 helix is the exchanged domain. Binding studies reveal an atypical BH3-binding profile, with sub-micromolar..
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Awarded by National Cancer Institute
Funding Acknowledgements
We thank G Hacker for the F1L cDNA; J Szarlat for computational and J Blyth and A Wardak for technical assistance; staff at the beamline ID23.1 at ESRF Grenoble for help with X-ray data collection; C3 Collaborative Crystallization Centre for assistance with crystallization; C Day, G Dewson, J Gulbis, G Hacker, M Hinds, E Lee, B Smith and I Street for discussions; and M Hinds for reagents. Our work is supported by scholarships, fellowships and grants from Cancer Council of Victoria (to PMC and WDF), NHMRC (Program Grant 257502; fellowships to DCSH, PMC and WDF), US NCI (CA80188 and CA43540), ARC (ADP0556836, LE0560722 and AB07CBT004 to MAP) and the Leukemia & Lymphoma Society (SCOR 7015-02; fellowship to MK).