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| | <StructureSection load='4uy2' size='340' side='right'caption='[[4uy2]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='4uy2' size='340' side='right'caption='[[4uy2]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4uy2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UY2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UY2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4uy2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus] 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=4UY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UY2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uxu|4uxu]], [[4d01|4d01]]</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=4uy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uy2 OCA], [https://pdbe.org/4uy2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uy2 RCSB], [https://www.ebi.ac.uk/pdbsum/4uy2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uy2 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4uy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uy2 OCA], [http://pdbe.org/4uy2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uy2 RCSB], [http://www.ebi.ac.uk/pdbsum/4uy2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uy2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/NXL1V_BUNMU NXL1V_BUNMU]] Produces peripheral paralysis by blocking neuromuscular transmission at the postsynaptic site. Binds to muscular and neuronal (alpha-7, alpha-8, and alpha-9) nicotinic acetylcholine receptors. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bungarus multicinctus]] | | [[Category: Bungarus multicinctus]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Giastas, P]] | + | [[Category: Giastas P]] |
| - | [[Category: Tzartos, S J]] | + | [[Category: Tzartos SJ]] |
| - | [[Category: Zarkadas, E]] | + | [[Category: Zarkadas E]] |
| - | [[Category: Zouridakis, M]] | + | [[Category: Zouridakis M]] |
| - | [[Category: Cys-loop receptor]]
| + | |
| - | [[Category: Ligand binding domain]]
| + | |
| - | [[Category: Toxin-binding protein-toxin complex]]
| + | |
| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
We determined the X-ray crystal structures of the extracellular domain (ECD) of the monomeric state of human neuronal alpha9 nicotinic acetylcholine receptor (nAChR) and of its complexes with the antagonists methyllycaconitine and alpha-bungarotoxin at resolutions of 1.8 A, 1.7 A and 2.7 A, respectively. The structure of the monomeric alpha9 ECD superimposed well with the structures of homologous proteins in pentameric assemblies, denoting native folding, despite the absence of a complementary subunit and transmembrane domain. The interaction motifs of both antagonists were similar to those in the complexes with homologous pentameric proteins, thus highlighting the major contribution of the principal side of alpha9 ECD to their binding. The structures revealed a functionally important beta7-beta10 strand interaction in alpha9-containing nAChRs, involving their unique Thr147, a hydration pocket similar to that of mouse alpha1 ECD and a membrane-facing network coordinated by the invariant Arg210.
Crystal structures of free and antagonist-bound states of human alpha9 nicotinic receptor extracellular domain.,Zouridakis M, Giastas P, Zarkadas E, Chroni-Tzartou D, Bregestovski P, Tzartos SJ Nat Struct Mol Biol. 2014 Oct 5. doi: 10.1038/nsmb.2900. PMID:25282151[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sgard F, Charpantier E, Bertrand S, Walker N, Caput D, Graham D, Bertrand D, Besnard F. A novel human nicotinic receptor subunit, alpha10, that confers functionality to the alpha9-subunit. Mol Pharmacol. 2002 Jan;61(1):150-9. PMID:11752216
- ↑ Nguyen VT, Ndoye A, Grando SA. Novel human alpha9 acetylcholine receptor regulating keratinocyte adhesion is targeted by Pemphigus vulgaris autoimmunity. Am J Pathol. 2000 Oct;157(4):1377-91. PMID:11021840
- ↑ Zouridakis M, Giastas P, Zarkadas E, Chroni-Tzartou D, Bregestovski P, Tzartos SJ. Crystal structures of free and antagonist-bound states of human alpha9 nicotinic receptor extracellular domain. Nat Struct Mol Biol. 2014 Oct 5. doi: 10.1038/nsmb.2900. PMID:25282151 doi:http://dx.doi.org/10.1038/nsmb.2900
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