3brd

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3brd, resolution 2.21Å ()
Ligands:
Gene: lag-1 (Caenorhabditis elegans), lin-12 (Caenorhabditis elegans)
Related: 3brf, 3brg
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml



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

Publication Abstract from PubMed

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.

RAM-induced allostery facilitates assembly of a notch pathway active transcription complex., Friedmann DR, Wilson JJ, Kovall RA, J Biol Chem. 2008 May 23;283(21):14781-91. Epub 2008 Apr 1. PMID:18381292

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

3brd is a 4 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA.

Reference

  • Friedmann DR, Wilson JJ, Kovall RA. RAM-induced allostery facilitates assembly of a notch pathway active transcription complex. J Biol Chem. 2008 May 23;283(21):14781-91. Epub 2008 Apr 1. PMID:18381292 doi:http://dx.doi.org/10.1074/jbc.M709501200

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