Phospholipid interaction sites in a ligand-gated ion channel from simulations and cryo-electron microscopy

Abstract

Ligand-gated ion channels (LGICs) are of crucial importance for electrochemical signal transduction in neurons and other excitable cells, where they open upon agonist binding in the extracellular domain. Evidence from a large number of channel families has attributed importance to lipids as allosteric modulators of channel function through interactions in the transmembrane domain. However, the structural and mechanistic details of such interactions remain elusive. Here, we quantified protein-lipid interactions in a pH-gated LGIC (GLIC), using a library of 460 μs atomistic molecular dynamics simulations.