1kcx

From Proteopedia

Revision as of 10:15, 20 March 2008

X-ray structure of NYSGRC target T-45

Overview

Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins involved in neuronal differentiation and axonal guidance. CRMP2 was previously shown to mediate the repulsive effect of Sema3A on axons and to participate in axonal specification. The X-ray crystal structure of murine CRMP1 was determined at 2.1 A resolution and demonstrates that CRMP1 is a bilobed 'lung-shaped' protein forming a tetrameric assembly. Structure-based mutagenesis of surface-exposed residues was employed to map functional domains. As a rapid assay for CRMP, we exploited a reconstituted Sema3A signaling system in COS-7 cells expressing the receptor components Neuropilin1 and PlexinA1 (NP1/PlexA1). In these cells, CRMP and PlexA1 form a physical complex that is reduced in amount by NP1 but enhanced by Sema3A/NP1. Furthermore, CRMP accelerates Sema3A-induced cell contraction. Alanine substitutions in one domain of CRMP1 produce a constitutively active protein that causes Sema3A-independent COS-7 contraction. This mutant CRMP mimics the DRG neurite outgrowth-inhibiting effects of Sema3A and reduces Sema3A-induced axonal repulsion. These data provide a structural view of CRMP function in Plex-dependent Sema3A signaling.

About this Structure

1KCX is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

Structural bases for CRMP function in plexin-dependent semaphorin3A signaling., Deo RC, Schmidt EF, Elhabazi A, Togashi H, Burley SK, Strittmatter SM, EMBO J. 2004 Jan 14;23(1):9-22. Epub 2003 Dec 18. PMID:14685275

Page seeded by OCA on Thu Mar 20 12:15:41 2008