1pb5
From Proteopedia
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NMR Structure of a Prototype LNR Module from Human Notch1
Contents |
Overview
Notch1 is a member of a conserved family of large modular heterodimeric, type 1 transmembrane receptors that control differentiation in, multicellular animals. Receptor maturation is accompanied by a, furin-dependent cleavage that converts the Notch1 precursor polypeptide, into a heterodimer consisting of an extracellular ligand-binding subunit, (NEC) and a transmembrane signaling subunit (NTM). Binding of a, physiologic ligand to NEC induces signaling by triggering additional, proteolytic cleavages in NTM, which allow its intracellular region to, translocate to the nucleus where it participates in a transcriptional, activation complex. In the absence of ligand, the three conserved LNR, modules of the NEC subunit participate in maintaining the receptor in its, resting conformation. Here, we report the solution structure of the first, LNR module (LNR_A) of human Notch1, and identify residues of LNR_A, perturbed by the presence of the adjacent module LNR_B. LNR_A is held, together by a unique arrangement of three disulfide bonds and a single, bound Ca(2+) ion, and adopts a novel fold that falls in the general class, of irregular disulfide-bonded structures. Residues perturbed by the, presence of the adjacent LNR_B module are predominantly hydrophobic, and, lie on one face of the module. These studies represent an initial step, toward understanding the structural interrelationships among the three, contiguous LNR modules required for proper regulation of Notch signaling.
Disease
Known diseases associated with this structure: Aortic valve disease OMIM:[190198], Leukemia, T-cell acute lymphoblastic OMIM:[190198]
About this Structure
1PB5 is a Single protein structure of sequence from Homo sapiens with CA as ligand. Full crystallographic information is available from OCA.
Reference
Nuclear magnetic resonance structure of a prototype Lin12-Notch repeat module from human Notch1., Vardar D, North CL, Sanchez-Irizarry C, Aster JC, Blacklow SC, Biochemistry. 2003 Jun 17;42(23):7061-7. PMID:12795601
Page seeded by OCA on Mon Nov 12 18:41:45 2007
