Structural Basis of Alcohol Inhibition of the Pentameric Ligand-Gated Ion Channel ELIC.

ABSTRACT: The structural basis for alcohol modulation of neuronal pentameric ligand-gated ion channels (pLGICs) remains elusive. We determined an inhibitory mechanism of alcohol on the pLGIC Erwinia chrysanthemi (ELIC) through direct binding to the pore. X-ray structures of ELIC co-crystallized with 2-bromoethanol, in both the absence and presence of agonist, reveal 2-bromoethanol binding in the pore near T237(6') and the extracellular domain (ECD) of each subunit at three different locations. Binding to the ECD does not appear to contribute to the inhibitory action of 2-bromoethanol and ethanol as indicated by the same functional responses of wild-type ELIC and mutants. In contrast, the ELIC-α1β3GABA_AR chimera, replacing the ELIC transmembrane domain (TMD) with the TMD of α1β3GABA_A<

SUBMITTER: Chen Q 

PROVIDER: S-EPMC5214846 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature