Regulation of pentameric ligand-gated ion channels by a semiconserved cation-pi interaction site

Abstract

Pentameric ligand-gated ion channels (pLGICs) are crucial mediators of electrochemical signal transduction in various organisms from bacteria to humans. While lipids were previously thought to mainly serve as a structural scaffold for protein stability, they are increasingly being recognized to play a significant role in regulating pLGIC function. However, the structural basis governing these lipid interactions remain poorly resolved. The bacterial channel ELIC has been identified to recapitulate several properties of eukaryotic pLGICs including activation by the neurotransmitter GABA and the binding/modulation by lipids - and thereby offers a simplified model system for structure-function relationship studies.