2ask
From Proteopedia
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Structure of human Artemin
Overview
Artemin (ART) promotes the growth of developing peripheral neurons by, signaling through a multicomponent receptor complex comprised of a, transmembrane tyrosine kinase receptor (cRET) and a specific, glycosylphosphatidylinositol-linked co-receptor (GFRalpha3). Glial cell, line-derived neurotrophic factor (GDNF) signals through a similar ternary, complex but requires heparan sulfate proteoglycans (HSPGs) for full, activity. HSPG has not been demonstrated as a requirement for ART, signaling. We crystallized ART in the presence of sulfate and solved its, structure by isomorphous replacement. The structure reveals ordered, sulfate anions bound to arginine residues in the pre-helix and, amino-terminal regions that were organized in a triad arrangement, characteristic of heparan sulfate. Three residues in the pre-helix were, singly or triply substituted with glutamic acid, and the resulting, proteins were shown to have reduced heparin-binding affinity that is, partly reflected in their ability to activate cRET. This study suggests, that ART binds HSPGs and identifies residues that may be involved in HSPG, binding.
About this Structure
2ASK is a Single protein structure of sequence from Homo sapiens with SO4 as ligand. Full crystallographic information is available from OCA.
Reference
Artemin crystal structure reveals insights into heparan sulfate binding., Silvian L, Jin P, Carmillo P, Boriack-Sjodin PA, Pelletier C, Rushe M, Gong B, Sah D, Pepinsky B, Rossomando A, Biochemistry. 2006 Jun 6;45(22):6801-12. PMID:16734417
Page seeded by OCA on Mon Nov 12 20:54:17 2007
