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101 a.a.
Key reference
DOI no: 10.1021/bi060035x Biochemistry 45:6801-6812 (2006) PubMed id: 16734417
Artemin crystal structure reveals insights into heparan sulfate binding. L.Silvian, P.Jin, P.Carmillo, P.A.Boriack-Sjodin, C.Pelletier, M.Rushe, B.Gong, D.Sah, B.Pepinsky, A.Rossomando. ABSTRACT
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.
Literature references that cite this PDB file's key reference
PubMed id Reference
18465825 M.D.Wood, G.H.Borschel, and S.E.Sakiyama-Elbert (2009).
Controlled release of glial-derived neurotrophic factor from fibrin matrices containing an affinity-based delivery system.J Biomed Mater Res A, 89, 909-918.
19090915 N.S.Gandhi, and R.L.Mancera (2008).
The structure of glycosaminoglycans and their interactions with proteins.Chem Biol Drug Des, 72, 455-482.
17013378 S.Schlee, P.Carmillo, and A.Whitty (2006).
Quantitative analysis of the activation mechanism of the multicomponent growth-factor receptor Ret.Nat Chem Biol, 2, 636-644. The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.
