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| | <StructureSection load='5kxi' size='340' side='right'caption='[[5kxi]], [[Resolution|resolution]] 3.94Å' scene=''> | | <StructureSection load='5kxi' size='340' side='right'caption='[[5kxi]], [[Resolution|resolution]] 3.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kxi]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KXI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KXI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kxi]] is a 5 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=5KXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KXI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NCT:(S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE'>NCT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.941Å</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]), CHRNB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NCT:(S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE'>NCT</scene></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=5kxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kxi OCA], [http://pdbe.org/5kxi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kxi RCSB], [http://www.ebi.ac.uk/pdbsum/5kxi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kxi 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=5kxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kxi OCA], [https://pdbe.org/5kxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kxi RCSB], [https://www.ebi.ac.uk/pdbsum/5kxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kxi 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. [[http://www.uniprot.org/uniprot/ACHB2_HUMAN ACHB2_HUMAN]] Defects in CHRNB2 are the cause of nocturnal frontal lobe epilepsy type 3 (ENFL3) [MIM:[http://omim.org/entry/605375 605375]]. ENFL3 is an autosomal dominant epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements.<ref>PMID:11062464</ref> <ref>PMID:11104662</ref> | + | [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> [[http://www.uniprot.org/uniprot/ACHB2_HUMAN ACHB2_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 sodiun 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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hibbs, R E]] | + | [[Category: Hibbs RE]] |
| - | [[Category: Morales-Perez, C L]] | + | [[Category: Morales-Perez CL]] |
| - | [[Category: Noviello, C M]] | + | [[Category: Noviello CM]] |
| - | [[Category: Acetylcholine receptor]]
| + | |
| - | [[Category: Cys-loop receptor]]
| + | |
| - | [[Category: Ligand-gated ion channel]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| 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
Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate fast chemical neurotransmission at the neuromuscular junction and have diverse signalling roles in the central nervous system. The nicotinic receptor has been a model system for cell-surface receptors, and specifically for ligand-gated ion channels, for well over a century. In addition to the receptors' prominent roles in the development of the fields of pharmacology and neurobiology, nicotinic receptors are important therapeutic targets for neuromuscular disease, addiction, epilepsy and for neuromuscular blocking agents used during surgery. The overall architecture of the receptor was described in landmark studies of the nicotinic receptor isolated from the electric organ of Torpedo marmorata. Structures of a soluble ligand-binding domain have provided atomic-scale insights into receptor-ligand interactions, while high-resolution structures of other members of the pentameric receptor superfamily provide touchstones for an emerging allosteric gating mechanism. All available high-resolution structures are of homopentameric receptors. However, the vast majority of pentameric receptors (called Cys-loop receptors in eukaryotes) present physiologically are heteromeric. Here we present the X-ray crystallographic structure of the human alpha4beta2 nicotinic receptor, the most abundant nicotinic subtype in the brain. This structure provides insights into the architectural principles governing ligand recognition, heteromer assembly, ion permeation and desensitization in this prototypical receptor class.
X-ray structure of the human alpha4beta2 nicotinic receptor.,Morales-Perez CL, Noviello CM, Hibbs RE Nature. 2016 Oct 3. doi: 10.1038/nature19785. PMID:27698419[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Morales-Perez CL, Noviello CM, Hibbs RE. X-ray structure of the human alpha4beta2 nicotinic receptor. Nature. 2016 Oct 3. doi: 10.1038/nature19785. PMID:27698419 doi:http://dx.doi.org/10.1038/nature19785
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