4ZLP: Crystal Structure Of Notch3 Negative Regulatory Region

Citation:
Abstract
Notch receptors are transmembrane proteins that undergo activating proteolysis in response to ligand stimulation. A negative regulatory region (NRR) maintains receptor quiescence by preventing protease cleavage prior to ligand binding. We report here the X-ray structure of the NRR of autoinhibited human Notch3, and compare it with the Notch1 and Notch2 NRRs. The overall architecture of the autoinhibited conformation, in which three LIN12-Notch repeat (LNR) modules wrap around a heterodimerization domain, is preserved in Notch3, but the autoinhibited conformation of the Notch3 NRR is less stable. The Notch3 NRR uses a highly conserved surface on the third LNR module to form a dimer in the crystal. Similar homotypic interfaces exist in Notch1 and Notch2. Together, these studies reveal distinguishing structural features associated with increased basal activity of Notch3, demonstrate increased ligand-independent signaling for disease-associated mutations that map to the Notch3 NRR, and identify a conserved dimerization interface present in multiple Notch receptors.
PDB ID: 4ZLPDownload
MMDB ID: 131930
PDB Deposition Date: 2015/5/1
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.48  Å
Source Organism:
Similar Structures:
Biological Unit for 4ZLP: dimeric; determined by author and by software (PISA)
Molecular Components in 4ZLP
Label Count Molecule
Proteins (2 molecules)
2
Neurogenic Locus Notch Homolog Protein 3(Gene symbol: NOTCH3)
Molecule annotation
Chemicals (16 molecules)
1
6
2
3
3
2
4
3
5
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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