2oo4

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Image:2oo4.gif

2oo4, resolution 2.003Å

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Structure of LNR-HD (Negative Regulatory Region) from human Notch 2

Contents

Overview

Notch receptors transmit signals between adjacent cells. Signaling is initiated when ligand binding induces metalloprotease cleavage of Notch within an extracellular negative regulatory region (NRR). We present here the X-ray structure of the human NOTCH2 NRR, which adopts an autoinhibited conformation. Extensive interdomain interactions within the NRR bury the metalloprotease site, showing that a substantial conformational movement is necessary to expose this site during activation by ligand. Leukemia-associated mutations in NOTCH1 probably release autoinhibition by destabilizing the conserved hydrophobic core of the NRR.

Disease

Known disease associated with this structure: Alagille syndrome 2 OMIM:[600275]

About this Structure

2OO4 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.

Reference

Structural basis for autoinhibition of Notch., Gordon WR, Vardar-Ulu D, Histen G, Sanchez-Irizarry C, Aster JC, Blacklow SC, Nat Struct Mol Biol. 2007 Apr;14(4):295-300. Epub 2007 Apr 1. PMID:17401372

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