Allosteric potentiation of a ligand-gated ion channel is mediated by access to a deep membrane-facing cavity.

ABSTRACT: Theories of general anesthesia have shifted in focus from bulk lipid effects to specific interactions with membrane proteins. Target receptors include several subtypes of pentameric ligand-gated ion channels; however, structures of physiologically relevant proteins in this family have yet to define anesthetic binding at high resolution. Recent cocrystal structures of the bacterial protein GLIC provide snapshots of state-dependent binding sites for the common surgical agent propofol (PFL), offering a detailed model system for anesthetic modulation. Here, we combine molecular dynamics and oocyte electrophysiology to reveal differential motion and modulation upon modification of a transmembrane binding site within each GLIC subunit. WT channels exhibited net inhibition by PFL, and a contracti

SUBMITTER: Heusser SA 

PROVIDER: S-EPMC6196478 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature