Structural basis for the ethanol action on G-protein-activated inwardly rectifying potassium channel 1 revealed by NMR spectroscopy.

ABSTRACT: Ethanol consumption leads to a wide range of pharmacological effects by acting on the signaling proteins in the human nervous system, such as ion channels. Despite its familiarity and biological importance, very little is known about the molecular mechanisms underlying the ethanol action, due to extremely weak binding affinity and the dynamic nature of the ethanol interaction. In this research, we focused on the primary in vivo target of ethanol, G-protein-activated inwardly rectifying potassium channel (GIRK), which is responsible for the ethanol-induced analgesia. By utilizing solution NMR spectroscopy, we characterized the changes in the structure and dynamics of GIRK induced by ethanol binding. We demonstrated here that ethanol binds to GIRK with an apparent dissociation constant of 1.

SUBMITTER: Toyama Y 

PROVIDER: S-EPMC5899474 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature