4URT

The crystal structure of a fragment of netrin-1 in complex with FN5- FN6 of DCC

4URT の概要

• エントリーDOI: 10.2210/pdb4urt/pdb
• 分子名称: NETRIN-1, NETRIN RECEPTOR DCC, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: protein binding, apoptosis, axon guidance, dependence receptor
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73801.99

構造登録者

Finci, L.I.,Krueger, N.,Sun, X.,Zhang, J.,Chegkazi, M.,Wu, Y.,Schenk, G.,Mertens, H.D.T.,Svergun, D.I.,Zhang, Y.,Wang, J.-h.,Meijers, R. (登録日: 2014-07-02, 公開日: 2014-09-10, 最終更新日: 2024-10-09)

主引用文献

Finci, L.I.,Krueger, N.,Sun, X.,Zhang, J.,Chegkazi, M.,Wu, Y.,Schenk, G.,Mertens, H.D.T.,Svergun, D.I.,Zhang, Y.,Wang, J.-H.,Meijers, R.
The Crystal Structure of Netrin-1 in Complex with Dcc Reveals the Bi-Functionality of Netrin-1 as a Guidance Cue
Neuron, 83:839-, 2014

PubMed 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.

PubMed: 25123307
DOI: 10.1016/J.NEURON.2014.07.010

実験手法

X-RAY DIFFRACTION (3.1 Å)