Paper Citing NAMD - Abstract
Bondarenko, Vasyl; Mowrey, David; Tillman, Tommy; Cui, Tanxing; Liu, Lu Tian; Xu, Yan; Tang, Pei
NMR structures of the transmembrane domains of the alpha 4 beta 2 nAChR
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1818:1261-1268, MAY 2012
The alpha 4 beta 2 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 alpha 4 beta 2 and other neuronal nAChRs is presently limited. In this study, we determined structures of the transmembrane (TM) domains of the alpha 4 and beta 2 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 Phi 4 and beta 2 interacted with each other and spontaneously formed pentameric assemblies in the LDAO micelles. The Na+ flux assay revealed that alpha 4 beta 2 formed Na+ permeable channels in lipid vesicles. Efflux of Na+ through the alpha 4 beta 2 channels reduced intra-vesicle Sodium Green (TM) fluorescence in a time-dependent manner that was not observed in vesicles without incorporating alpha 4 beta 2. The study provides structural insight into the TM domains of the alpha 4 beta 2 nAChR. It offers a valuable structural framework for rationalizing extensive biochemical data collected previously on the alpha 4 beta 2 nAChR and for designing new therapeutic modulators. (C) 2012 Elsevier B.V. All rights reserved.
