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Structural insights into the degradation of Mcl-1 induced by BH3 domains.

ABSTRACT: 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.

SUBMITTER: Czabotar PE

PROVIDER: S-EPMC1851040 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Structural insights into the degradation of Mcl-1 induced by BH3 domains.

Czabotar Peter E PE Lee Erinna F EF van Delft Mark F MF Day Catherine L CL Smith Brian J BJ Huang David C S DC Fairlie W Douglas WD Hinds Mark G MG Colman Peter M PM

Proceedings of the National Academy of Sciences of the United States of America 20070327 15

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-termi ...[more]

PMID: 17389404

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