Structural basis for the modulation of pentameric ligand-gated ion channel function by lipids

Abstract

Pentameric ligand-gated ion channels (pLGICs) play a central role in synaptic communication and are implicated in a plethora of neurological disorders leading to human disease. Membrane lipids are known to modulate pLGIC function, but the mechanisms underlying their effects are poorly understood. Recent structures reveal sites for the binding of membrane lipids to pLGICs, thus providing a structural basis for interpreting functional data on pLGIC-lipid interactions. Here, we review the literature describing the known functional effects of membrane lipids on different members of the pLGIC superfamily and highlight pLGIC structures that exhibit bound lipids. We discuss new insight into the mechanisms of pLGIC-lipid interactions that has been derived from these recent structures.

Keywords: Allosteric modulation; Annular; Lipid binding sites; Lipid-protein interactions; Non-annular; Pentameric ligand-gated ion channels.