2oo4 | pdb_00002oo4
Structure of LNR-HD (Negative Regulatory Region) from human Notch 2
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. 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 Page seeded by OCA on Sun May 4 11:18:20 2008
