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1: Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6217-22. Epub 2007 Mar 27.Click here to read Click here to read Links

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

Czabotar PE, Lee EF, van Delft MF, Day CL, Smith BJ, Huang DC, Fairlie WD, Hinds MG, Colman PM.

The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.

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.

PMID: 17389404 [PubMed - indexed for MEDLINE]

PMCID: PMC1851040

Structures reported by this article