Structural Insights into the Degradation of Mcl-1 Induced by BH3 Domains
Journal Article
·
· Proceedings of the National Academy of Sciences of the USA
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.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 930351
- Report Number(s):
- BNL-81067-2008-JA; PNASA6; TRN: US200904%%643
- Journal Information:
- Proceedings of the National Academy of Sciences of the USA, Vol. 104, Issue 15; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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