Completing the family portrait of the anti-apoptotic Bcl-2 proteins: Crystal structure of human Bfl-1 in complex with Bim

Herman, Maria DoloresStockholms universitet,Institutionen för biokemi och biofysik (author)

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.

Nyman, TomasKarolinska Institutet (author)
Welin, Martin (author)
Lehtiö, LariKarolinska Institutet (author)
Flodin, Susanne (author)
Trésaugues, Lionel (author)
Kotenyova, Tetyana (author)
Flores, Alex (author)
Nordlund, PärKarolinska Institutet (author)
Stockholms universitetInstitutionen för biokemi och biofysik (creator_code:org_t)

By the author/editor: Herman, Maria Do ...; Nyman, Tomas; Welin, Martin; Lehtiö, Lari; Flodin, Susanne; Trésaugues, Lion ...; show more...; Kotenyova, Tetya ...; Flores, Alex; Nordlund, Pär; show less...

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