Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA

Jeffrey J Wilson; Rhett A Kovall

doi:10.1016/j.cell.2006.01.035

Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA

Cell. 2006 Mar 10;124(5):985-96. doi: 10.1016/j.cell.2006.01.035.

Authors

Jeffrey J Wilson¹, Rhett A Kovall

Affiliation

¹ Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

PMID: 16530045
DOI: 10.1016/j.cell.2006.01.035

Abstract

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 A 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.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amino Acid Sequence
Animals
Crystallography, X-Ray
DNA / chemistry
DNA / metabolism*
DNA-Binding Proteins / chemistry*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Humans
Macromolecular Substances
Models, Molecular
Molecular Sequence Data
Nuclear Proteins / chemistry*
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Protein Structure, Secondary
Protein Structure, Tertiary*
Receptors, Notch / chemistry*
Receptors, Notch / genetics
Receptors, Notch / metabolism
Repressor Proteins / metabolism
Sequence Alignment
Signal Transduction / physiology*
Static Electricity
Trans-Activators
Transcription Factors / chemistry*
Transcription Factors / genetics
Transcription Factors / metabolism
Transcription, Genetic
Transcriptional Activation*

Substances

DNA-Binding Proteins
MAML1 protein, human
Macromolecular Substances
Nuclear Proteins
Receptors, Notch
Repressor Proteins
Trans-Activators
Transcription Factors
DNA

Associated data

PDB/2FO1