View source for 5nmz


==human Neurturin (97-197)==
<StructureSection load='5nmz' size='340' side='right'caption='[[5nmz]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nmz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NMZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NMZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5nmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nmz OCA], [https://pdbe.org/5nmz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nmz RCSB], [https://www.ebi.ac.uk/pdbsum/5nmz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nmz ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/NRTN_HUMAN NRTN_HUMAN] Hirschsprung disease. Genetic variations in NRTN may contribute to Hirschsprung disease, in association with mutations of RET gene, and possibly mutations in other loci. Hirschsprung disease is a disorder of neural crest development is characterized by the absence of intramural ganglion cells in the hindgut, often resulting in intestinal obstruction.<ref>PMID:9700200</ref> 
== Function ==
[https://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.
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== 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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5nmz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bigalke JM]]
[[Category: Roth R]]
[[Category: Sandmark J]]