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

Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3428-33. 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

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


  • Bcl-2 protein, Human herpesvirus 8
  • Membrane Proteins
  • Oncogene Proteins
  • Peptide Fragments
  • Proto-Oncogene Proteins c-bcl-2
  • Solutions
  • Viral Proteins
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-X Protein

Associated data

  • PDB/1K3K