2MAW

NMR structures of the alpha7 nAChR transmembrane domain.


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 25 
  • 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

Insights into distinct modulation of alpha 7 and alpha 7 beta 2 nicotinic acetylcholine receptors by the volatile anesthetic isoflurane.

Mowrey, D.D.Liu, Q.Bondarenko, V.Chen, Q.Seyoum, E.Xu, Y.Wu, J.Tang, P.

(2013) J Biol Chem 288: 35793-35800

  • DOI: https://doi.org/10.1074/jbc.M113.508333
  • Primary Citation of Related Structures:  
    2MAW

  • PubMed Abstract: 

    Nicotinic acetylcholine receptors (nAChRs) are targets of general anesthetics, but functional sensitivity to anesthetic inhibition varies dramatically among different subtypes of nAChRs. Potential causes underlying different functional responses to anesthetics remain elusive. Here we show that in contrast to the α7 nAChR, the α7β2 nAChR is highly susceptible to inhibition by the volatile anesthetic isoflurane in electrophysiology measurements. Isoflurane-binding sites in β2 and α7 were found at the extracellular and intracellular end of their respective transmembrane domains using NMR. Functional relevance of the identified β2 site was validated via point mutations and subsequent functional measurements. Consistent with their functional responses to isoflurane, β2 but not α7 showed pronounced dynamics changes, particularly for the channel gate residue Leu-249(9'). These results suggest that anesthetic binding alone is not sufficient to generate functional impact; only those sites that can modulate channel dynamics upon anesthetic binding will produce functional effects.


  • Organizational Affiliation

    From the Departments of Anesthesiology.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Neuronal acetylcholine receptor subunit alpha-7137Homo sapiensMutation(s): 9 
Gene Names: CHRFAM7ACHRNA7NACHRA7
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P36544 (Homo sapiens)
Explore P36544 
Go to UniProtKB:  P36544
PHAROS:  P36544
GTEx:  ENSG00000175344 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP36544
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 25 
  • 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: 2013-11-13
    Type: Initial release
  • Version 1.1: 2014-05-07
    Changes: Database references
  • Version 1.2: 2023-06-14
    Changes: Data collection, Database references, Other