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

Huang Q, Petros AM, Virgin HW, Fesik SW, Olejniczak ET
Proc Natl Acad Sci U S A. 2002 99 (6): 3428-33

PMID: 11904405 · PMCID: PMC122540 · DOI:10.1073/pnas.062525799

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-x(L) 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-x(L) and Bcl-2, suggesting that the viral protein has evolved to have a different mechanism of action than the host proteins.

MeSH Terms (22)

Amino Acid Sequence Apoptosis bcl-2 Homologous Antagonist-Killer Protein bcl-X Protein Herpesvirus 8, Human Hydrophobic and Hydrophilic Interactions Membrane Proteins Models, Molecular Molecular Sequence Data Mutation Nuclear Magnetic Resonance, Biomolecular Oncogene Proteins Peptide Fragments Protein Binding Protein Structure, Quaternary Protein Structure, Secondary Proto-Oncogene Proteins c-bcl-2 Sequence Alignment Sequence Homology, Amino Acid Solutions Substrate Specificity Viral Proteins

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