Crystal Structure of the CSL-Notch-Mastermind Ternary Complex Bound to DNA
Notch signaling mediates communication between cells and is essential for proper embryonic patterning and development. CSL is a DNA binding transcription factor that regulates transcription of Notch target genes by interacting with coregulators. Transcriptional activation requires the displacement of corepressors from CSL by the intracellular portion of the receptor Notch (NotchIC) and the recruitment of the coactivator protein Mastermind to the complex. Here we report the 3.1 {angstrom} structure of the ternary complex formed by CSL, NotchIC, and Mastermind bound to DNA. As expected, the RAM domain of Notch interacts with the {beta} trefoil domain of CSL; however, the C-terminal domain of CSL has an unanticipated central role in the interface formed with the Notch ankyrin repeats and Mastermind. Ternary complex formation induces a substantial conformational change within CSL, suggesting a molecular mechanism for the conversion of CSL from a repressor to an activator.
- 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:
- 930233
- Report Number(s):
- BNL-80908-2008-JA; CELLB5; TRN: US200822%%1411
- Journal Information:
- Cell, Vol. 124; ISSN 0092-8674
- Country of Publication:
- United States
- Language:
- English
Similar Records
RAM-Induced Allostery Facilitates Assembly of a Notch Pathway Active Transcription Complex
Structural Basis for Cooperativity in Recruitment of MAML Co-activators to Notch Transcription Complexes