6FKQ

THE CRYSTAL STRUCTURE OF A FRAGMENT OF NETRIN-1 IN COMPLEX WITH A FRAGMENT OF DRAXIN

Summary for 6FKQ

• Entry DOI: 10.2210/pdb6fkq/pdb
• Related: 4URT
• Related PRD ID: PRD_900017
• Descriptor: Netrin-1, Draxin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: axon guidance cue, netrin-1, draxin, commissural neuron, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 51699.61

Authors

Bhowmick, T.,Meijers, R. (deposition date: 2018-01-24, release date: 2018-03-21, Last modification date: 2024-01-17)

Primary citation

Liu, Y.,Bhowmick, T.,Liu, Y.,Gao, X.,Mertens, H.D.T.,Svergun, D.I.,Xiao, J.,Zhang, Y.,Wang, J.H.,Meijers, R.
Structural Basis for Draxin-Modulated Axon Guidance and Fasciculation by Netrin-1 through DCC.
Neuron, 97:1261-1267.e4, 2018

PubMed Abstract: Axon guidance involves the spatiotemporal interplay between guidance cues and membrane-bound cell-surface receptors, present on the growth cone of the axon. Netrin-1 is a prototypical guidance cue that binds to deleted in colorectal cancer (DCC), and it has been proposed that the guidance cue Draxin modulates this interaction. Here, we present structural snapshots of Draxin/DCC and Draxin/Netrin-1 complexes, revealing a triangular relationship that affects Netrin-mediated haptotaxis and fasciculation. Draxin interacts with DCC through the N-terminal four immunoglobulin domains, and Netrin-1 through the EGF-3 domain, in the same region where DCC binds. Netrin-1 and DCC bind to adjacent sites on Draxin, which appears to capture Netrin-1 and tether it to the DCC receptor. We propose the conformational flexibility of the single-pass membrane receptor DCC is used to promote fasciculation and regulate axon guidance through concerted Netrin-1/Draxin binding. VIDEO ABSTRACT.

PubMed: 29503192
DOI: 10.1016/j.neuron.2018.02.010

Experimental method

X-RAY DIFFRACTION (3.07 Å)