6fkq
From Proteopedia
THE CRYSTAL STRUCTURE OF A FRAGMENT OF NETRIN-1 IN COMPLEX WITH A FRAGMENT OF DRAXIN
Structural highlights
Function[NET1_HUMAN] Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. It also serve as a survival factor via its association with its receptors which prevent the initiation of apoptosis. Involved in tumorigenesis by regulating apoptosis.[1] [DRAXI_HUMAN] Chemorepulsive axon guidance protein required for the development of spinal cord and forebrain commissures. Acts as a chemorepulsive guidance protein for commissural axons during development. Able to inhibit or repel neurite outgrowth from dorsal spinal cord. Inhibits the stabilization of cytosolic beta-catenin (CTNNB1) via its interaction with LRP6, thereby acting as an antagonist of Wnt signaling pathway.[HAMAP-Rule:MF_03060] Publication Abstract from PubMedAxon 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. Structural Basis for Draxin-Modulated Axon Guidance and Fasciculation by Netrin-1 through DCC.,Liu Y, Bhowmick T, Liu Y, Gao X, Mertens HDT, Svergun DI, Xiao J, Zhang Y, Wang JH, Meijers R Neuron. 2018 Feb 20. pii: S0896-6273(18)30109-0. doi:, 10.1016/j.neuron.2018.02.010. PMID:29503192[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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