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| ==NMR structures of the second transmembrane domain of the neuronal acetylcholine receptor beta 2 subunit== | | ==NMR structures of the second transmembrane domain of the neuronal acetylcholine receptor beta 2 subunit== |
- | <StructureSection load='2k59' size='340' side='right'caption='[[2k59]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2k59' size='340' side='right'caption='[[2k59]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[2k59]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K59 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K59 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2k59]] 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=2K59 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K59 FirstGlance]. <br> |
- | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2k58|2k58]]</div></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'>[https://proteopedia.org/fgij/fg.htm?mol=2k59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k59 OCA], [https://pdbe.org/2k59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k59 RCSB], [https://www.ebi.ac.uk/pdbsum/2k59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k59 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=2k59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k59 OCA], [https://pdbe.org/2k59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k59 RCSB], [https://www.ebi.ac.uk/pdbsum/2k59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k59 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease == | | == Disease == |
- | [[https://www.uniprot.org/uniprot/ACHB2_HUMAN ACHB2_HUMAN]] Defects in CHRNB2 are the cause of nocturnal frontal lobe epilepsy type 3 (ENFL3) [MIM:[https://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/ACHB2_HUMAN ACHB2_HUMAN] Defects in CHRNB2 are the cause of nocturnal frontal lobe epilepsy type 3 (ENFL3) [MIM:[https://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> |
| == Function == | | == Function == |
- | [[https://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/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> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| ==See Also== | | ==See Also== |
- | *[[Nicotinic Acetylcholine Receptor|Nicotinic Acetylcholine Receptor]] | + | *[[Acetyl choline receptor 3D structures|Acetyl choline receptor 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| + | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Bondarenko, V]] | + | [[Category: Bondarenko V]] |
- | [[Category: Tang, P]] | + | [[Category: Tang P]] |
- | [[Category: Xu, Y]] | + | [[Category: Xu Y]] |
- | [[Category: Yushmanov, V]] | + | [[Category: Yushmanov V]] |
- | [[Category: Beta 2 subunit]]
| + | |
- | [[Category: Cell junction]]
| + | |
- | [[Category: Disease mutation]]
| + | |
- | [[Category: Epilepsy]]
| + | |
- | [[Category: Glycoprotein]]
| + | |
- | [[Category: Ion transport]]
| + | |
- | [[Category: Ionic channel]]
| + | |
- | [[Category: Membrane]]
| + | |
- | [[Category: Neuronal acetylcholine receptor]]
| + | |
- | [[Category: Polymorphism]]
| + | |
- | [[Category: Postsynaptic cell membrane]]
| + | |
- | [[Category: Second transmembrane domain]]
| + | |
- | [[Category: Synapse]]
| + | |
- | [[Category: Transmembrane]]
| + | |
- | [[Category: Transport]]
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- | [[Category: Transport protein]]
| + | |
| Structural highlights
Disease
ACHB2_HUMAN Defects in CHRNB2 are the cause of nocturnal frontal lobe epilepsy type 3 (ENFL3) [MIM:605375. ENFL3 is an autosomal dominant epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements.[1] [2]
Function
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.[3]
Publication Abstract from PubMed
Structure and backbone dynamics of a selectively [(15)N]Leu-labeled 28-residue segment of the extended second transmembrane domain (TM2e) of the human neuronal nicotinic acetylcholine receptor (nAChR) beta(2) subunit were studied by (1)H and (15)N solution-state NMR in dodecylphosphocholine micelles. The TM2e structure was determined on the basis of the nuclear Overhauser effects (NOEs) and the hydrogen bond restraints, which were inferred from the presence of H(alpha)(i)-H(N)(i+3), H(alpha)(i)-H(beta)(i+3), and H(alpha)(i)-H(N)(i+4) NOE connectivity and from the slow amide hydrogen exchange with D(2)O. The TM2e structure of the nAChR beta(2) subunit contains a helical region between T4 and K22. Backbone dynamics were calculated using the model-free approach based on the (15)N relaxation rate constants, R(1) and R(2), and on the (15)N-[(1)H] NOE. The data acquired at 9.4 and 14.1 T and calculations using different dynamic models demonstrated no conformational exchange and internal motions on the nanosecond time scale. The global tumbling time of TM2e in micelles was 14.4 +/- 0.2 ns; the NOE values were greater than 0.63 at 9.4 T, and the order parameter, S(2), was 0.83-0.96 for all (15)N-labeled leucine residues, suggesting a restricted internal motion. This is the first report of NMR structure and backbone dynamics of the second transmembrane domain of the human nAChR beta(2) subunit in a membrane-mimetic environment, providing the basis for subsequent studies of subunit interactions in the transmembrane domain complex of the neuronal nAChR.
NMR structure and dynamics of the second transmembrane domain of the neuronal acetylcholine receptor beta 2 subunit.,Yushmanov VE, Xu Y, Tang P Biochemistry. 2003 Nov 11;42(44):13058-65. PMID:14596621[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ De Fusco M, Becchetti A, Patrignani A, Annesi G, Gambardella A, Quattrone A, Ballabio A, Wanke E, Casari G. The nicotinic receptor beta 2 subunit is mutant in nocturnal frontal lobe epilepsy. Nat Genet. 2000 Nov;26(3):275-6. PMID:11062464 doi:10.1038/81566
- ↑ Phillips HA, Favre I, Kirkpatrick M, Zuberi SM, Goudie D, Heron SE, Scheffer IE, Sutherland GR, Berkovic SF, Bertrand D, Mulley JC. CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy. Am J Hum Genet. 2001 Jan;68(1):225-31. Epub 2000 Dec 5. PMID:11104662 doi:10.1086/316946
- ↑ 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
- ↑ Yushmanov VE, Xu Y, Tang P. NMR structure and dynamics of the second transmembrane domain of the neuronal acetylcholine receptor beta 2 subunit. Biochemistry. 2003 Nov 11;42(44):13058-65. PMID:14596621 doi:10.1021/bi0350396
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