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| | ==NMR structures of the transmembrane domains of the nAChR a4 subunit== | | ==NMR structures of the transmembrane domains of the nAChR a4 subunit== |
| - | <StructureSection load='2lly' size='340' side='right' caption='[[2lly]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2lly' size='340' side='right'caption='[[2lly]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2lly]] 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=2LLY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LLY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2lly]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LLY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LLY FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lm2|2lm2]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2lm2|2lm2]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHRNA4, NACRA4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHRNA4, NACRA4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2lly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lly OCA], [http://pdbe.org/2lly PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lly RCSB], [http://www.ebi.ac.uk/pdbsum/2lly PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2lly 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=2lly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lly OCA], [https://pdbe.org/2lly PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lly RCSB], [https://www.ebi.ac.uk/pdbsum/2lly PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lly ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ACHA4_HUMAN ACHA4_HUMAN]] Autosomal dominant nocturnal frontal lobe epilepsy. The disease is caused by mutations affecting the gene represented in this entry. | + | [[https://www.uniprot.org/uniprot/ACHA4_HUMAN ACHA4_HUMAN]] Autosomal dominant nocturnal frontal lobe epilepsy. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACHA4_HUMAN ACHA4_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 permeable to sodium ions.<ref>PMID:22361591</ref> | + | [[https://www.uniprot.org/uniprot/ACHA4_HUMAN ACHA4_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 permeable to sodium ions.<ref>PMID:22361591</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: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Bondarenko, V]] | | [[Category: Bondarenko, V]] |
| | [[Category: Cui, T]] | | [[Category: Cui, T]] |
| Structural highlights
Disease
[ACHA4_HUMAN] Autosomal dominant nocturnal frontal lobe epilepsy. The disease is caused by mutations affecting the gene represented in this entry.
Function
[ACHA4_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 permeable to sodium ions.[1]
Publication Abstract from PubMed
The alpha4beta2 nicotinic acetylcholine receptor (nAChR) is the predominant heteromeric subtype of nAChRs in the brain, which has been implicated in numerous neurological conditions. The structural information specifically for the alpha4beta2 and other neuronal nAChRs is presently limited. In this study, we determined structures of the transmembrane (TM) domains of the alpha4 and beta2 subunits in lauryldimethylamine-oxide (LDAO) micelles using solution NMR spectroscopy. NMR experiments and size exclusion chromatography-multi-angle light scattering (SEC-MALS) analysis demonstrated that the TM domains of alpha4 and beta2 interacted with each other and spontaneously formed pentameric assemblies in the LDAO micelles. The Na(+) flux assay revealed that alpha4beta2 formed Na(+) permeable channels in lipid vesicles. Efflux of Na(+) through the alpha4beta2 channels reduced intra-vesicle Sodium Green fluorescence in a time-dependent manner that was not observed in vesicles without incorporating alpha4beta2. The study provides structural insight into the TM domains of the alpha4beta2 nAChR. It offers a valuable structural framework for rationalizing extensive biochemical data collected previously on the alpha4beta2 nAChR and for designing new therapeutic modulators.
NMR structures of the transmembrane domains of the alpha4beta2 nAChR.,Bondarenko V, Mowrey D, Tillman T, Cui T, Liu LT, Xu Y, Tang P Biochim Biophys Acta. 2012 Feb 14;1818(5):1261-1268. PMID:22361591[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bondarenko V, Mowrey D, Tillman T, Cui T, Liu LT, Xu Y, Tang P. NMR structures of the transmembrane domains of the alpha4beta2 nAChR. Biochim Biophys Acta. 2012 Feb 14;1818(5):1261-1268. PMID:22361591 doi:10.1016/j.bbamem.2012.02.008
- ↑ Bondarenko V, Mowrey D, Tillman T, Cui T, Liu LT, Xu Y, Tang P. NMR structures of the transmembrane domains of the alpha4beta2 nAChR. Biochim Biophys Acta. 2012 Feb 14;1818(5):1261-1268. PMID:22361591 doi:10.1016/j.bbamem.2012.02.008
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