| Structural highlights
Function
ARTN_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 PubMed
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.
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
- ↑ Baloh RH, Tansey MG, Lampe PA, Fahrner TJ, Enomoto H, Simburger KS, Leitner ML, Araki T, Johnson EM Jr, Milbrandt J. Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex. Neuron. 1998 Dec;21(6):1291-302. PMID:9883723
- ↑ Masure S, Geerts H, Cik M, Hoefnagel E, Van Den Kieboom G, Tuytelaars A, Harris S, Lesage AS, Leysen JE, Van Der Helm L, Verhasselt P, Yon J, Gordon RD. Enovin, a member of the glial cell-line-derived neurotrophic factor (GDNF) family with growth promoting activity on neuronal cells. Existence and tissue-specific expression of different splice variants. Eur J Biochem. 1999 Dec;266(3):892-902. PMID:10583383
- ↑ Silvian L, Jin P, Carmillo P, Boriack-Sjodin PA, Pelletier C, Rushe M, Gong B, Sah D, Pepinsky B, Rossomando A. Artemin crystal structure reveals insights into heparan sulfate binding. Biochemistry. 2006 Jun 6;45(22):6801-12. PMID:16734417 doi:10.1021/bi060035x
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