PNAS Plus: From the Cover: A gating mechanism of pentameric ligand-gated ion channels

Significance Pentameric ligand-gated ion channels (pLGICs) control membrane conductance in living systems from bacteria to humans. Molecular dynamics simulations based on the structures of the prokaryotic channels from Gloeobacter violaceus (GLIC) and Erwinia chrysanthemi (ELIC) and the eukaryotic channel from Caenorhabditis elegans (GluCl) show that the open-to-closed transition begins with a major quaternary (twisting) transition which is followed by tertiary relaxation of the pore-forming helices. The latter is initiated by the outward tilting of the extracellular β-sandwiches in response to agonist unbinding. The proposed atomic resolution mechanism for channel gating, which is in accord with the Monod–Wyman–Changeux model of allostery, is expected to be generally applicable to pLGICs.