Structural insights into the degradation of Mcl-1 induced by BH3 domains.
Czabotar P.E., Lee E.F., van Delft M.F., Day C.L., Smith B.J., Huang D.C.S., Fairlie W.D., Hinds M.G., Colman P.M.
Apoptosis is held in check by prosurvival proteins of the Bcl-2 family. The distantly related BH3-only proteins bind to and antagonize them, thereby promoting apoptosis. Whereas binding of the BH3-only protein Noxa to prosurvival Mcl-1 induces Mcl-1 degradation by the proteasome, binding of another BH3-only ligand, Bim, elevates Mcl-1 protein levels. We compared the three-dimensional structures of the complexes formed between BH3 peptides of both Bim and Noxa, and we show that a discrete C-terminal sequence of the Noxa BH3 is necessary to instigate Mcl-1 degradation.
Proc. Natl. Acad. Sci. U.S.A. 104:6217-6222(2007) [PubMed] [Europe PMC]