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2lm2

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Current revision

NMR structures of the transmembrane domains of the AChR b2 subunit

Structural highlights

2lm2 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2lm2"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2lm2]] 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=2LM2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LM2 FirstGlance]. <br>
-</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=2lm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lm2 OCA], [https://pdbe.org/2lm2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lm2 RCSB], [https://www.ebi.ac.uk/pdbsum/2lm2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lm2 ProSAT]</span></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=2lm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lm2 OCA], [https://pdbe.org/2lm2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lm2 RCSB], [https://www.ebi.ac.uk/pdbsum/2lm2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lm2 ProSAT]</span></td></tr>
 </table>
 == Disease ==

2lm2

From Proteopedia

Current revision

NMR structures of the transmembrane domains of the AChR b2 subunit

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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