PDBsum entry 4urt

Protein binding

PDB id: 4urt

Contents

Protein chains

420 a.a.

206 a.a.

Ligands

NAG-NAG ×3

SO4 ×17

GOL

Metals

_CA

_CL

PDB id:

4urt

Name:

Protein binding

Title:

The crystal structure of a fragment of netrin-1 in complex with fn5- fn6 of dcc

Structure:

Netrin-1. Chain: a. Fragment: vi and v domains, residues 39-453. Synonym: epididymis tissue protein li 131p. Netrin receptor dcc. Chain: b. Fragment: fn5-fn6, residues 844-1043. Synonym: colorectal cancer suppressor, immunoglobulin superfamily dcc subclass member 1, tumor suppressor protein dcc, deleted in

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606

Resolution:

3.10Å R-factor: 0.231 R-free: 0.265

Authors:

L.I.Finci,N.Krueger,X.Sun,J.Zhang,M.Chegkazi,Y.Wu,G.Schenk, H.D.T.Mertens,D.I.Svergun,Y.Zhang,J.-H.Wang,R.Meijers

Key ref:

L.I.Finci et al. (2014). The crystal structure of netrin-1 in complex with DCC reveals the bifunctionality of netrin-1 as a guidance cue. Neuron, 83, 839-849. PubMed id: 25123307 DOI: 10.1016/j.neuron.2014.07.010

Date:

02-Jul-14 Release date: 10-Sep-14

Protein chain

O95631  (NET1_HUMAN) -  Netrin-1 from Homo sapiens

Seq: 604 a.a.

Struc: 420 a.a.*

Protein chain

P43146  (DCC_HUMAN) -  Netrin receptor DCC from Homo sapiens

Seq: 1447 a.a.

Struc: 206 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

DOI no: 10.1016/j.neuron.2014.07.010

Neuron 83:839-849 (2014)

PubMed id: 25123307

The crystal structure of netrin-1 in complex with DCC reveals the bifunctionality of netrin-1 as a guidance cue.

L.I.Finci, N.Krüger, X.Sun, J.Zhang, M.Chegkazi, Y.Wu, G.Schenk, H.D.Mertens, D.I.Svergun, Y.Zhang, J.H.Wang, R.Meijers.

ABSTRACT

Netrin-1 is a guidance cue that can trigger either attraction or repulsion effects on migrating axons of neurons, depending on the repertoire of receptors available on the growth cone. How a single chemotropic molecule can act in such contradictory ways has long been a puzzle at the molecular level. Here we present the crystal structure of netrin-1 in complex with the Deleted in Colorectal Cancer (DCC) receptor. We show that one netrin-1 molecule can simultaneously bind to two DCC molecules through a DCC-specific site and through a unique generic receptor binding site, where sulfate ions staple together positively charged patches on both DCC and netrin-1. Furthermore, we demonstrate that UNC5A can replace DCC on the generic receptor binding site to switch the response from attraction to repulsion. We propose that the modularity of binding allows for the association of other netrin receptors at the generic binding site, eliciting alternative turning responses.