Completing the family portrait of the anti-apoptotic Bcl-2 proteins: Crystal structure of human Bfl-1 in complex with Bim
2008 (English)In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 582, no 25-26, 3590-3594 p.Article in journal (Refereed) Published
Evasion of apoptosis is recognized as a characteristic of malignant growth. Anti-apoptotic B-cell lymphoma-2 (Bcl-2) family members have therefore emerged as potential therapeutic targets due to their critical role in proliferating cancer cells. Here, we present the crystal structure of Bfl-1, the last anti-apoptotic Bcl-2 family member to be structurally characterized, in complex with a peptide corresponding to the BH3 region of the pro-apoptotic protein Bim. The structure reveals distinct features at the peptide-binding site, likely to define the binding specificity for pro-apoptotic proteins. Superposition of the Bfl-1:Bim complex with that of Mcl-1:Bim reveals a significant local plasticity of hydrophobic interactions contributed by the Bim peptide, likely to be the basis for the multi specificity of Bim for anti-apoptotic proteins.
Place, publisher, year, edition, pages
2008. Vol. 582, no 25-26, 3590-3594 p.
Apoptosis, B-cell lymphoma-2, Cancer, Bfl-1; A1, Crystal structure
IdentifiersURN: urn:nbn:se:su:diva-25483DOI: 10.1016/j.febslet.2008.09.028ISI: 000260807500004OAI: oai:DiVA.org:su-25483DiVA: diva2:199816