6hy7
From Proteopedia
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(New page: '''Unreleased structure''' The entry 6hy7 is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of alpha9 nAChR extracellular domain in complex with alpha-conotoxin RgIA== | |
| + | <StructureSection load='6hy7' size='340' side='right'caption='[[6hy7]], [[Resolution|resolution]] 2.26Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6hy7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_regius Conus regius] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HY7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HY7 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]] 2.26Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AAR:ARGININEAMIDE'>AAR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6hy7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hy7 OCA], [https://pdbe.org/6hy7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hy7 RCSB], [https://www.ebi.ac.uk/pdbsum/6hy7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hy7 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ACHA9_HUMAN ACHA9_HUMAN] Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma. May also regulate keratinocyte adhesion.<ref>PMID:11752216</ref> <ref>PMID:11021840</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The alpha9 subunit of nicotinic acetylcholine receptors (nAChRs) exists mainly in heteropentameric assemblies with alpha10. Accumulating data indicate the presence of three different binding sites in alpha9alpha10 nAChRs: the alpha9(+)/alpha9(-), the alpha9(+)/alpha10(-), and the alpha10(+)/alpha9(-). The major role of the principal (+) side of the extracellular domain (ECD) of alpha9 subunit in binding of the antagonists methyllylcaconitine and alpha-bungarotoxin was shown previously by the crystal structures of the monomeric alpha9-ECD with these molecules. Here we present the 2.26-A resolution crystal structure of alpha9-ECD in complex with alpha-conotoxin (alpha-Ctx) RgIA, a potential drug for chronic pain, the first structure reported for a complex between an nAChR domain and an alpha-Ctx. Superposition of this structure with those of other alpha-Ctxs bound to the homologous pentameric acetylcholine binding proteins revealed significant similarities in the orientation of bound conotoxins, despite the monomeric state of the alpha9-ECD. In addition, ligand-binding studies calculated a binding affinity of RgIA to the alpha9-ECD at the low micromolar range. Given the high identity between alpha9 and alpha10 ECDs, particularly at their (+) sides, the presented structure was used as template for molecular dynamics simulations of the ECDs of the human alpha9alpha10 nAChR in pentameric assemblies. Our results support a favorable binding of RgIA at alpha9(+)/alpha9(-) or alpha10(+)/alpha9(-) rather than the alpha9(+)/alpha10(-) interface, in accordance with previous mutational and functional data. | ||
| - | + | Crystal Structure of the Monomeric Extracellular Domain of alpha9 Nicotinic Receptor Subunit in Complex With alpha-Conotoxin RgIA: Molecular Dynamics Insights Into RgIA Binding to alpha9alpha10 Nicotinic Receptors.,Zouridakis M, Papakyriakou A, Ivanov IA, Kasheverov IE, Tsetlin V, Tzartos S, Giastas P Front Pharmacol. 2019 May 1;10:474. doi: 10.3389/fphar.2019.00474. eCollection, 2019. PMID:31118896<ref>PMID:31118896</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6hy7" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Acetyl choline receptor 3D structures|Acetyl choline receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Conus regius]] | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Giastas P]] | ||
| + | [[Category: Zouridakis M]] | ||
Current revision
Crystal structure of alpha9 nAChR extracellular domain in complex with alpha-conotoxin RgIA
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