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Solution structure of a Bcl-2 homolog from Kaposi sarcoma virus

By Qiulong Huang, Andrew M. Petros, Herbert W. Virgin, Stephen W. Fesik and Edward T. Olejniczak

Abstract

Kaposi sarcoma-associated herpes virus (KSHV) contains a gene that has functional and sequence homology to the apoptotic Bcl-2 family of proteins [Sarid, R., Sato, T., Bohenzky, R. A., Russo, J. J. & Chang, Y. (1997) Nat. Med. 3, 293–298]. The viral Bcl-2 protein promotes survival of infected cells and may contribute to the development of Kaposi sarcoma tumors [Boshoff, C. & Chang, Y. (2001) Annu. Rev. Med. 52, 453–470]. Here we describe the solution structure of the viral Bcl-2 homolog from KSHV. Comparison of the KSHV Bcl-2 structure to that of Bcl-2 and Bcl-xL shows that although the overall fold is the same, there are key differences in the lengths of the helices and loops. Binding studies on peptides derived from the Bcl-2 homology region 3 of proapoptotic family members indicate that the specificity of the viral protein is very different from what was previously observed for Bcl-xL and Bcl-2, suggesting that the viral protein has evolved to have a different mechanism of action than the host proteins

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 2002
DOI identifier: 10.1073/pnas.062525799
OAI identifier: oai:pubmedcentral.nih.gov:122540
Provided by: PubMed Central
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