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| | ==NMR structures of the alpha7 nAChR transmembrane domain.== | | ==NMR structures of the alpha7 nAChR transmembrane domain.== |
| - | <StructureSection load='2maw' size='340' side='right' caption='[[2maw]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2maw' size='340' side='right'caption='[[2maw]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2maw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MAW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2maw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MAW FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHRFAM7A, CHRNA7, NACHRA7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2maw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2maw OCA], [http://pdbe.org/2maw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2maw RCSB], [http://www.ebi.ac.uk/pdbsum/2maw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2maw ProSAT]</span></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=2maw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2maw OCA], [https://pdbe.org/2maw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2maw RCSB], [https://www.ebi.ac.uk/pdbsum/2maw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2maw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ACHA7_HUMAN ACHA7_HUMAN]] 15q13.3 microdeletion syndrome. | + | [https://www.uniprot.org/uniprot/ACHA7_HUMAN ACHA7_HUMAN] 15q13.3 microdeletion syndrome. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACHA7_HUMAN ACHA7_HUMAN]] After binding acetylcholine, the AChR responds by 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 blocked by alpha-bungarotoxin. | + | [https://www.uniprot.org/uniprot/ACHA7_HUMAN ACHA7_HUMAN] After binding acetylcholine, the AChR responds by 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 blocked by alpha-bungarotoxin. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bondarenko, V]] | + | [[Category: Large Structures]] |
| - | [[Category: Mowrey, D]] | + | [[Category: Bondarenko V]] |
| - | [[Category: Tang, P]] | + | [[Category: Mowrey D]] |
| - | [[Category: Xu, Y]] | + | [[Category: Tang P]] |
| - | [[Category: Membrane protein]]
| + | [[Category: Xu Y]] |
| - | [[Category: Transmembrane domain]]
| + | |
| Structural highlights
Disease
ACHA7_HUMAN 15q13.3 microdeletion syndrome.
Function
ACHA7_HUMAN After binding acetylcholine, the AChR responds by 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 blocked by alpha-bungarotoxin.
Publication Abstract from PubMed
Nicotinic acetylcholine receptors (nAChRs) are targets of general anesthetics, but functional sensitivity to anesthetic inhibition varies dramatically among different subtypes of nAChRs. Potential causes underlying different functional responses to anesthetics remain elusive. Here we show that in contrast to the alpha7 nAChR, the alpha7beta2 nAChR is highly susceptible to inhibition by the volatile anesthetic isoflurane in electrophysiology measurements. Isoflurane-binding sites in beta2 and alpha7 were found at the extracellular and intracellular end of their respective transmembrane domains using NMR. Functional relevance of the identified beta2 site was validated via point mutations and subsequent functional measurements. Consistent with their functional responses to isoflurane, beta2 but not alpha7 showed pronounced dynamics changes, particularly for the channel gate residue Leu-249(9'). These results suggest that anesthetic binding alone is not sufficient to generate functional impact; only those sites that can modulate channel dynamics upon anesthetic binding will produce functional effects.
Insights into distinct modulation of alpha7 and alpha7beta2 nicotinic acetylcholine receptors by the volatile anesthetic isoflurane.,Mowrey DD, Liu Q, Bondarenko V, Chen Q, Seyoum E, Xu Y, Wu J, Tang P J Biol Chem. 2013 Dec 13;288(50):35793-800. doi: 10.1074/jbc.M113.508333. Epub, 2013 Nov 5. PMID:24194515[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mowrey DD, Liu Q, Bondarenko V, Chen Q, Seyoum E, Xu Y, Wu J, Tang P. Insights into distinct modulation of alpha7 and alpha7beta2 nicotinic acetylcholine receptors by the volatile anesthetic isoflurane. J Biol Chem. 2013 Dec 13;288(50):35793-800. doi: 10.1074/jbc.M113.508333. Epub, 2013 Nov 5. PMID:24194515 doi:http://dx.doi.org/10.1074/jbc.M113.508333
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