PDBsum entry 4bqc

Cell adhesion

PDB id: 4bqc

Contents

Protein chains

197 a.a.

176 a.a.

Ligands

GU4-YYJ ×2

NAG

Metals

_NA ×2

PDB id:

4bqc

Name:

Cell adhesion

Title:

Crystal structure of the fn5 and fn6 domains of neo1 bound to sos

Structure:

Neogenin. Chain: a, b. Fragment: fn-type iii domains 5 and 6, residues 883-1133. Engineered: yes. Other_details: n-linked glycosylation at n940

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t.

Resolution:

3.20Å R-factor: 0.219 R-free: 0.259

Authors:

C.H.Bell,E.Healey,S.Vanerp,B.Bishop,C.Tang,R.J.C.Gilbert, A.R.Aricescu,R.J.Pasterkamp,C.Siebold

Key ref:

C.H.Bell et al. (2013). Structure of the repulsive guidance molecule (RGM)-neogenin signaling hub. Science, 341, 77-80. PubMed id: 23744777 DOI: 10.1126/science.1232322

Date:

30-May-13 Release date: 12-Jun-13

Protein chain

P97798  (NEO1_MOUSE) -  Neogenin from Mus musculus

Seq: 1492 a.a.

Struc: 197 a.a.*

Protein chain

P97798  (NEO1_MOUSE) -  Neogenin from Mus musculus

Seq: 1492 a.a.

Struc: 176 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1126/science.1232322

Science 341:77-80 (2013)

PubMed id: 23744777

Structure of the repulsive guidance molecule (RGM)-neogenin signaling hub.

C.H.Bell, E.Healey, S.van Erp, B.Bishop, C.Tang, R.J.Gilbert, A.R.Aricescu, R.J.Pasterkamp, C.Siebold.

ABSTRACT

Repulsive guidance molecule family members (RGMs) control fundamental and diverse cellular processes, including motility and adhesion, immune cell regulation, and systemic iron metabolism. However, it is not known how RGMs initiate signaling through their common cell-surface receptor, neogenin (NEO1). Here, we present crystal structures of the NEO1 RGM-binding region and its complex with human RGMB (also called dragon). The RGMB structure reveals a previously unknown protein fold and a functionally important autocatalytic cleavage mechanism and provides a framework to explain numerous disease-linked mutations in RGMs. In the complex, two RGMB ectodomains conformationally stabilize the juxtamembrane regions of two NEO1 receptors in a pH-dependent manner. We demonstrate that all RGM-NEO1 complexes share this architecture, which therefore represents the core of multiple signaling pathways.