2ask
From Proteopedia
Structure of human Artemin
Structural highlights
FunctionARTN_HUMAN Ligand for the GFR-alpha-3-RET receptor complex but can also activate the GFR-alpha-1-RET receptor complex. Supports the survival of sensory and sympathetic peripheral neurons in culture and also supports the survival of dopaminergic neurons of the ventral mid-brain. Strong attractant of gut hematopoietic cells thus promoting the formation Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedArtemin (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. 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Boriack-Sjodin PA | Carmillo P | Gong BJ | Jin P | Pelletier C | Pepinsky B | Rossomando A | Rushe M | Sah D | Silvian L
