5mr5
From Proteopedia
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==Ligand-receptor complex.== | ==Ligand-receptor complex.== | ||
| - | <StructureSection load='5mr5' size='340' side='right' caption='[[5mr5]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='5mr5' size='340' side='right'caption='[[5mr5]], [[Resolution|resolution]] 2.00Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5mr5]] is a 4 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[5mr5]] 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=5MR5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MR5 FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5mr5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mr5 OCA], [https://pdbe.org/5mr5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mr5 RCSB], [https://www.ebi.ac.uk/pdbsum/5mr5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mr5 ProSAT]</span></td></tr> |
</table> | </table> | ||
== Disease == | == 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 == | == 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. |
| + | <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/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: Aagaard | + | [[Category: Large Structures]] |
| - | [[Category: Dahl | + | [[Category: Aagaard A]] |
| - | [[Category: Oster | + | [[Category: Dahl G]] |
| - | [[Category: Roth | + | [[Category: Oster L]] |
| - | [[Category: Sandmark | + | [[Category: Roth R]] |
| - | + | [[Category: Sandmark J]] | |
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Current revision
Ligand-receptor complex.
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Categories: Homo sapiens | Large Structures | Aagaard A | Dahl G | Oster L | Roth R | Sandmark J
