4URT

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

Summary for 4URT

• Entry DOI: 10.2210/pdb4urt/pdb
• Descriptor: 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)
• Functional Keywords: protein binding, apoptosis, axon guidance, dependence receptor
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 73801.99

Authors

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. (deposition date: 2014-07-02, release date: 2014-09-10, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.1 Å)