Solution structure of a Bcl-2 homolog from Kaposi sarcoma virus.
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.
Huang
Qiulong
Q
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
Petros
Andrew M
AM
Virgin
Herbert W
HW
Fesik
Stephen W
SW
Olejniczak
Edward T
ET
D000595:Amino Acid Sequence; D017209:Apoptosis; D019288:Herpesvirus 8, Human / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D015513:Oncogene Proteins; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D013379:Substrate Specificity; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein
C452184:Bcl-2 protein, Human herpesvirus 8; D008565:Membrane Proteins; D015513:Oncogene Proteins; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D012996:Solutions; D014764:Viral Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein