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5mr5
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/NRTN_HUMAN NRTN_HUMAN]] Supports the survival of sympathetic neurons in culture. May regulate the development and maintenance of the CNS. Might control the size of non-neuronal cell population such as haemopoietic cells. [[http://www.uniprot.org/uniprot/GFRA2_HUMAN GFRA2_HUMAN]] Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor. Isoform 2: participates in NRTN-induced 'Ser-727' phosphorylation of STAT3.[UniProtKB:O08842] | [[http://www.uniprot.org/uniprot/NRTN_HUMAN NRTN_HUMAN]] Supports the survival of sympathetic neurons in culture. May regulate the development and maintenance of the CNS. Might control the size of non-neuronal cell population such as haemopoietic cells. [[http://www.uniprot.org/uniprot/GFRA2_HUMAN GFRA2_HUMAN]] Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor. Isoform 2: participates in NRTN-induced 'Ser-727' phosphorylation of STAT3.[UniProtKB:O08842] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Neurturin (NRTN) provides trophic support to neurons and is considered a therapeutic agent for neurodegenerative diseases, such as Parkinson's disease. It binds to its co-receptor GFRa2 and the resulting NRTN:GFRa2 complex activates the transmembrane receptors RET or NCAM. We report the crystal structure of NRTN, alone and in complex with GFRa2. This is the first crystal structure of a GFRa with all three domains and shows that domain 1 does not interact directly with NRTN, but may support an interaction with RET and/or NCAM, via a highly conserved surface. In addition, biophysical results show that the relative concentration of GFRa2 on cell surfaces can affect the functional affinity of NRTN through avidity effects. We have identified a heparan sulfate binding site on NRTN and a putative binding site in GFRa2, suggesting that heparan sulfate has a role in assembly of the signalling complex. We further show that mutant NRTN with reduced affinity for heparan sulfate may provide a route forward for delivery of NRTN with increased exposure in preclinical in vivo models and ultimately to Parkinson's patients. | ||
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| + | Structure and biophysical characterisation of the human full-length Neurturin-GFRa2 complex - a role for heparan sulfate in signalling.,Sandmark J, Dahl G, Oster L, Xu B, Johansson P, Akerud T, Aagaard A, Davidsson P, Bigalke JM, Sorhede-Winzell M, Rainey GJ, Roth RG J Biol Chem. 2018 Feb 2. pii: RA117.000820. doi: 10.1074/jbc.RA117.000820. PMID:29414779<ref>PMID:29414779</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5mr5" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 07:43, 22 February 2018
Ligand-receptor complex.
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Categories: Human | Aagaard, A | Dahl, G | Oster, L | Roth, R | Sandmark, J | Complex | Ligand-receptor complex | Receptor | Signaling protein | Signalling
