2LM2

NMR structures of the transmembrane domains of the AChR b2 subunit

Summary for 2LM2

• Entry DOI: 10.2210/pdb2lm2/pdb
• Related: 2LLY
• NMR Information: BMRB: 18096
• Descriptor: Neuronal acetylcholine receptor subunit beta-2 (1 entity in total)
• Functional Keywords: acetylcholine receptor, transmembrane domain, transport protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein: P17787
• Total number of polymer chains: 1
• Total formula weight: 15085.80

Authors

Bondarenko, V.,Mowrey, D.,Tillman, T.,Cui, T.,Liu, L.T.,Xu, Y.,Tang, P. (deposition date: 2011-11-18, release date: 2012-03-28, Last modification date: 2024-05-15)

Primary citation

Bondarenko, V.,Mowrey, D.,Tillman, T.,Cui, T.,Liu, L.T.,Xu, Y.,Tang, P.
NMR structures of the transmembrane domains of the a4b2 nAChR.
Biochim.Biophys.Acta, 1818:1261-1268, 2012

PubMed Abstract: The α4β2 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 α4β2 and other neuronal nAChRs is presently limited. In this study, we determined structures of the transmembrane (TM) domains of the α4 and β2 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 α4 and β2 interacted with each other and spontaneously formed pentameric assemblies in the LDAO micelles. The Na(+) flux assay revealed that α4β2 formed Na(+) permeable channels in lipid vesicles. Efflux of Na(+) through the α4β2 channels reduced intra-vesicle Sodium Green™ fluorescence in a time-dependent manner that was not observed in vesicles without incorporating α4β2. The study provides structural insight into the TM domains of the α4β2 nAChR. It offers a valuable structural framework for rationalizing extensive biochemical data collected previously on the α4β2 nAChR and for designing new therapeutic modulators.

PubMed: 22361591
DOI: 10.1016/j.bbamem.2012.02.008

Experimental method

SOLUTION NMR