4zlp | pdb_00004zlp

Crystal Structure of Notch3 Negative Regulatory Region

spinqualitylabelsall models 4zlp, resolution 2.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zlp is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CA, GOL, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease NOTC3_HUMAN CADASIL;Infantile myofibromatosis. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function NOTC3_HUMAN Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). Publication Abstract from PubMed 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. Insights into Autoregulation of Notch3 from Structural and Functional Studies of Its Negative Regulatory Region.,Xu X, Choi SH, Hu T, Tiyanont K, Habets R, Groot AJ, Vooijs M, Aster JC, Chopra R, Fryer C, Blacklow SC Structure. 2015 Jul 7;23(7):1227-35. doi: 10.1016/j.str.2015.05.001. Epub 2015, Jun 4. PMID:26051713 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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