2VJ3

Human Notch-1 EGFs 11-13

Summary for 2VJ3

• Entry DOI: 10.2210/pdb2vj3/pdb
• Related: 1PB5 1TOZ 1YYH 2F8X 2F8Y
• Descriptor: NEUROGENIC LOCUS NOTCH HOMOLOG PROTEIN 1, CALCIUM ION, SODIUM ION, ... (5 entities in total)
• Functional Keywords: transcription, metal-binding, transmembrane, developmental protein, notch signaling pathway, differentiation, phosphorylation, egf-like domain, transcription regulation, receptor, activator, ank repeat, signalling, polymorphism, glycoprotein, extracellular, egf, notch, jagged, nucleus, calcium, membrane
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 15134.80

Authors

Johnson, S.,Cordle, J.,Tay, J.Z.,Roversi, P.,Lea, S.M. (deposition date: 2007-12-06, release date: 2008-07-29, Last modification date: 2023-12-13)

Primary citation

Cordle, J.,Johnson, S.,Tay, J.Z.,Roversi, P.,Wilkin, M.B.,De Madrid, B.H.,Shimizu, H.,Jensen, S.,Whiteman, P.,Jin, B.,Redfield, C.,Baron, M.,Lea, S.M.,Handford, P.A.
A Conserved Face of the Jagged/Serrate Dsl Domain is Involved in Notch Trans-Activation and Cis-Inhibition.
Nat.Struct.Mol.Biol., 15:849-, 2008

PubMed Abstract: The Notch receptor and its ligands are key components in a core metazoan signaling pathway that regulates the spatial patterning, timing and outcome of many cell-fate decisions. Ligands contain a disulfide-rich Delta/Serrate/LAG-2 (DSL) domain required for Notch trans-activation or cis-inhibition. Here we report the X-ray structure of a receptor binding region of a Notch ligand, the DSL-EGF3 domains of human Jagged-1 (J-1(DSL-EGF3)). The structure reveals a highly conserved face of the DSL domain, and we show, by functional analysis of Drosophila melanogster ligand mutants, that this surface is required for both cis- and trans-regulatory interactions with Notch. We also identify, using NMR, a surface of Notch-1 involved in J-1(DSL-EGF3) binding. Our data imply that cis- and trans-regulation may occur through the formation of structurally distinct complexes that, unexpectedly, involve the same surfaces on both ligand and receptor.

PubMed: 18660822
DOI: 10.1038/NSMB.1457

Experimental method

X-RAY DIFFRACTION (2.6 Å)