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3brd

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Revision as of 06:33, 24 April 2008 by OCA (Talk | contribs)
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Template:STRUCTURE 3brd

CSL (Lag-1) bound to DNA with Lin-12 RAM peptide, P212121


Overview

The Notch pathway is a conserved cell-to-cell signaling mechanism, in which extracellular signals are transduced into transcriptional outputs through the nuclear effector CSL. CSL is converted from a repressor to an activator through the formation of the CSL-NotchIC-Mastermind ternary complex. The RAM domain of NotchIC avidly interacts with CSL; however, its role in assembly of the CSL-NotchIC-Mastermind ternary complex is not understood. Here we provide a comprehensive thermodynamic, structural, and biochemical analysis of the RAM-CSL interaction for components from both mouse and worm. Our binding data shows that RAM and CSL form a high affinity complex in the presence or absence of DNA. Our structural studies reveal a striking distal conformational change in CSL upon RAM binding, which creates a docking site for Mastermind to bind to the complex. Finally, we show that the addition of a RAM peptide in trans facilitates formation of the CSL-NotchIC-Mastermind ternary complex in vitro.

About this Structure

3BRD is a Protein complex structure of sequences from Caenorhabditis elegans. Full crystallographic information is available from OCA.

Reference

RAM induced allostery facilitates assembly of a notch pathway active transcription complex., Friedmann DR, Wilson JJ, Kovall RA, J Biol Chem. 2008 Apr 1;. PMID:18381292 Page seeded by OCA on Thu Apr 24 09:33:18 2008

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