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Title: Crystal Structure of the CSL-Notch-Mastermind Ternary Complex Bound to DNA

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 {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.

Authors:
;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930233
Report Number(s):
BNL-80908-2008-JA
Journal ID: ISSN 0092-8674; CELLB5; TRN: US200822%%1411
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cell; Journal Volume: 124
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; COMMUNICATIONS; CONFORMATIONAL CHANGES; CONVERSION; CRYSTAL STRUCTURE; DNA; GENES; INTERFACES; PROTEINS; RECEPTORS; TARGETS; TRANSCRIPTION; TRANSCRIPTION FACTORS; national synchrotron light source

Citation Formats

Wilson,J., and Kovall, R.. Crystal Structure of the CSL-Notch-Mastermind Ternary Complex Bound to DNA. United States: N. p., 2006. Web. doi:10.1016/j.cell.2006.01.035.
Wilson,J., & Kovall, R.. Crystal Structure of the CSL-Notch-Mastermind Ternary Complex Bound to DNA. United States. doi:10.1016/j.cell.2006.01.035.
Wilson,J., and Kovall, R.. Sun . "Crystal Structure of the CSL-Notch-Mastermind Ternary Complex Bound to DNA". United States. doi:10.1016/j.cell.2006.01.035.
@article{osti_930233,
title = {Crystal Structure of the CSL-Notch-Mastermind Ternary Complex Bound to DNA},
author = {Wilson,J. and Kovall, R.},
abstractNote = {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.},
doi = {10.1016/j.cell.2006.01.035},
journal = {Cell},
number = ,
volume = 124,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}
  • No abstract prepared.
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