PMID- 22361591
OWN - NLM
STAT- MEDLINE
DCOM- 20130426
LR  - 20211021
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Electronic)
IS  - 0006-3002 (Linking)
VI  - 1818
IP  - 5
DP  - 2012 May
TI  - NMR structures of the transmembrane domains of the alpha4beta2 nAChR.
PG  - 1261-8
LID - 10.1016/j.bbamem.2012.02.008 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Bondarenko, Vasyl
AU  - Bondarenko V
AD  - Department of Anesthesiology, University of Pittsburgh, School of Medicine, PA 
      15260, USA.
FAU - Mowrey, David
AU  - Mowrey D
FAU - Tillman, Tommy
AU  - Tillman T
FAU - Cui, Tanxing
AU  - Cui T
FAU - Liu, Lu Tian
AU  - Liu LT
FAU - Xu, Yan
AU  - Xu Y
FAU - Tang, Pei
AU  - Tang P
LA  - eng
GR  - R37GM049202/GM/NIGMS NIH HHS/United States
GR  - R56 GM056257/GM/NIGMS NIH HHS/United States
GR  - R01GM56257/GM/NIGMS NIH HHS/United States
GR  - R01 GM056257-13/GM/NIGMS NIH HHS/United States
GR  - R01 GM066358-10/GM/NIGMS NIH HHS/United States
GR  - R37 GM049202/GM/NIGMS NIH HHS/United States
GR  - R01 GM066358/GM/NIGMS NIH HHS/United States
GR  - R37 GM049202-18/GM/NIGMS NIH HHS/United States
GR  - R01 GM056257/GM/NIGMS NIH HHS/United States
GR  - R01 GM066358-08S1/GM/NIGMS NIH HHS/United States
GR  - R56 GM056257-10A1/GM/NIGMS NIH HHS/United States
GR  - R01GM66358/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120214
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Dimethylamines)
RN  - 0 (Micelles)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (nicotinic receptor alpha4beta2)
RN  - 4F6FC4MI8W (dodecyldimethylamine oxide)
RN  - 9NEZ333N27 (Sodium)
SB  - IM
MH  - Dimethylamines/chemistry
MH  - Humans
MH  - Ion Transport/physiology
MH  - Micelles
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Protein Structure, Quaternary
MH  - Protein Structure, Tertiary
MH  - Receptors, Nicotinic/*chemistry/metabolism
MH  - Sodium/chemistry/metabolism
PMC - PMC3319252
MID - NIHMS357732
EDAT- 2012/03/01 06:00
MHDA- 2013/04/27 06:00
PMCR- 2013/05/01
CRDT- 2012/02/25 06:00
PHST- 2011/12/20 00:00 [received]
PHST- 2012/01/30 00:00 [revised]
PHST- 2012/02/07 00:00 [accepted]
PHST- 2012/02/25 06:00 [entrez]
PHST- 2012/03/01 06:00 [pubmed]
PHST- 2013/04/27 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - S0005-2736(12)00059-4 [pii]
AID - 10.1016/j.bbamem.2012.02.008 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2012 May;1818(5):1261-8. doi: 10.1016/j.bbamem.2012.02.008. 
      Epub 2012 Feb 14.