1PB5

NMR Structure of a Prototype LNR Module from Human Notch1

Summary for 1PB5

• Entry DOI: 10.2210/pdb1pb5/pdb
• NMR Information: BMRB: 5817
• Descriptor: Neurogenic locus notch homolog protein 1, CALCIUM ION (2 entities in total)
• Functional Keywords: notch signaling, lin12/notch repeat, calcium-binding domain, protein module, disulfide bond, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein (By similarity). Notch 1 intracellular domain: Nucleus (By similarity): P46531
• Total number of polymer chains: 1
• Total formula weight: 3758.04

Authors

Vardar, D.,North, C.L.,Sanchez-Irizarry, C.,Aster, J.C.,Blacklow, S.C. (deposition date: 2003-05-14, release date: 2003-06-17, Last modification date: 2024-10-09)

Primary citation

Vardar, D.,North, C.L.,Sanchez-Irizarry, C.,Aster, J.C.,Blacklow, S.C.
Nuclear Magnetic Resonance Structure of a Prototype Lin12-Notch Repeat Module from Human Notch1
Biochemistry, 42:7061-7067, 2003

PubMed Abstract: 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.

PubMed: 12795601
DOI: 10.1021/bi034156y

Experimental method

SOLUTION NMR