PDBsum entry 2vj3

Transcription

PDB id: 2vj3

Contents

Protein chain

120 a.a. *

Metals

_CL ×2

_CA ×4

_NA ×2

Waters ×23

* Residue conservation analysis

PDB id:

2vj3

Name:

Transcription

Title:

Human notch-1 egfs 11-13

Structure:

Neurogenic locus notch homolog protein 1. Chain: a. Fragment: egfs 11-13, residues 411-526. Synonym: notch 1, hn1, translocation-associated notch protein tan-1, notch-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.60Å R-factor: 0.239 R-free: 0.244

Authors:

S.Johnson,J.Cordle,J.Z.Tay,P.Roversi,S.M.Lea

Key ref:

J.Cordle et al. (2008). A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition. Nat Struct Biol, 15, 849-857. PubMed id: 18660822 DOI: 10.1038/nsmb.1457

Date:

06-Dec-07 Release date: 29-Jul-08

Protein chain

P46531  (NOTC1_HUMAN) -  Neurogenic locus notch homolog protein 1 from Homo sapiens

Seq: 2555 a.a.

Struc: 120 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1038/nsmb.1457

Nat Struct Biol 15:849-857 (2008)

PubMed id: 18660822

A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition.

J.Cordle, S.Johnson, J.Z.Tay, P.Roversi, M.B.Wilkin, B.H.de Madrid, H.Shimizu, S.Jensen, P.Whiteman, B.Jin, C.Redfield, M.Baron, S.M.Lea, P.A.Handford.

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.

Selected figure(s)

Figure 2.
(a) The overall structure of J-1[DSL-EGF3] is shown in a cartoon representation colored from blue at the N terminus (residue 187) to red at the C terminus (residue 335). Disulfide bonds are shown in yellow stick representations, and two views differing by a rotation of 90° about the long axis are shown. (b) Stereo view of the DSL domain fold. (c) Sequences of the four J-1[DSL-EGF3] domains with disulfide bond pairings indicated. (d) Crystallographic structure of N-1[11–13] shown as in a. The bound Ca^2+ in each EGF domain is shown in a space-filling representation. All structural figures were generated with PyMol (http://www.pymol.org/).

Figure 3.
Analysis of an alignment of the Jagged/Delta family DSL domains representing various species (H. sapiens Jagged-1, residues 187–229; D. melanogaster Serrate, residues 237–279; H. sapiens Jagged-2, residues 198–240; H. sapiens Delta-like 1, residues 179–221; D. melanogaster Delta, residues 184–226; H. sapiens Delta-like 4, residues 175–217; C. elegans LAG-2, residues 124–166; H. sapiens Delta-like 3, residues 178–215) (a) and the DSL structure (b) reveals a series of highly conserved, but surface-exposed, residues. Residues that are conserved and predicted to form a Notch binding face are shown in red, cysteines in yellow and a nonconserved residue on the opposite face in blue. (c) Electrostatic surface potential of J-1[DSL-EGF3] and N-1[11–13] plotted at 4 kT e^-1 using APBS^54. Note the positively charged patch (blue) within the DSL domain of Jagged-1 and the negatively charged surface (red) of Notch. The surfaces predicted by sequence/structure analysis (J-1[DSL-EGF3]) and NMR studies (N-1[11–13]) to be involved in binding are highlighted by green bands.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Nat Struct Biol (2008, 15, 849-857) copyright 2008.

Figures were selected by an automated process.