3BRF

CSL (Lag-1) bound to DNA with Lin-12 RAM peptide, C2221

Summary for 3BRF

• Entry DOI: 10.2210/pdb3brf/pdb
• Related: 3BRD 3BRG
• Descriptor: DNA (5'-D(*DTP*DTP*DAP*DCP*DTP*DGP*DTP*DGP*DGP*DGP*DAP*DAP*DAP*DGP*DA)-3'), DNA (5'-D(*DAP*DAP*DTP*DCP*DTP*DTP*DTP*DCP*DCP*DCP*DAP*DCP*DAP*DGP*DT)-3'), Lin-12 and glp-1 phenotype protein 1, isoform a, ... (6 entities in total)
• Functional Keywords: protein-dna complex, signaling, transcription, notch, dna-binding, ank repeat, developmental protein, differentiation, egf-like domain, glycoprotein, membrane, transmembrane, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Caenorhabditis elegans; More
• Total number of polymer chains: 4
• Total formula weight: 65040.04

Authors

Wilson, J.J.,Kovall, R.A. (deposition date: 2007-12-21, release date: 2008-04-01, Last modification date: 2024-02-21)

Primary citation

Friedmann, D.R.,Wilson, J.J.,Kovall, R.A.
RAM-induced Allostery Facilitates Assembly of a Notch Pathway Active Transcription Complex.
J.Biol.Chem., 283:14781-14791, 2008

PubMed Abstract: 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 (RBP-J associated molecule) 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 show 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.

PubMed: 18381292
DOI: 10.1074/jbc.M709501200

Experimental method

X-RAY DIFFRACTION (2.47 Å)