2LLY

NMR structures of the transmembrane domains of the nAChR a4 subunit


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

NMR structures of the transmembrane domains of the a4b2 nAChR.

Bondarenko, V.Mowrey, D.Tillman, T.Cui, T.Liu, L.T.Xu, Y.Tang, P.

(2012) Biochim Biophys Acta 1818: 1261-1268

  • DOI: https://doi.org/10.1016/j.bbamem.2012.02.008
  • Primary Citation of Related Structures:  
    2LLY, 2LM2

  • 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.


  • Organizational Affiliation

    Department of Anesthesiology, University of Pittsburgh, School of Medicine, PA 15260, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Neuronal acetylcholine receptor subunit alpha-4137Homo sapiensMutation(s): 7 
Gene Names: CHRNA4NACRA4
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P43681 (Homo sapiens)
Explore P43681 
Go to UniProtKB:  P43681
PHAROS:  P43681
GTEx:  ENSG00000101204 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP43681
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-03-28
    Type: Initial release
  • Version 1.1: 2023-06-14
    Changes: Data collection, Database references, Other
  • Version 1.2: 2024-05-15
    Changes: Data collection, Database references