2oo4
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Notch receptors transmit signals between adjacent cells. Signaling is | + | 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. |
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| + | ==Disease== | ||
| + | Known disease associated with this structure: Alagille syndrome 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600275 600275]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Aster, J | + | [[Category: Aster, J C.]] |
| - | [[Category: Blacklow, S | + | [[Category: Blacklow, S C.]] |
| - | [[Category: Gordon, W | + | [[Category: Gordon, W R.]] |
[[Category: Histen, G.]] | [[Category: Histen, G.]] | ||
[[Category: Sanchez-Irizarry, C.]] | [[Category: Sanchez-Irizarry, C.]] | ||
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[[Category: alpha-beta-sandwich; sea domain; lnr; lin12 notch repeat; cysteine-rich; hd domain]] | [[Category: alpha-beta-sandwich; sea domain; lnr; lin12 notch repeat; cysteine-rich; hd domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:20:38 2008'' |
Revision as of 16:20, 21 February 2008
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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
Page seeded by OCA on Thu Feb 21 18:20:38 2008
