Ion channels as lipid sensors: from structures to mechanisms

Ion channels play critical roles in cellular function by facilitating the flow of ions across the membrane in response to chemical or mechanical stimuli. Ion channels operate in a lipid bilayer, which can modulate or define their function. Recent technical advancements have led to the solution of numerous ion channel structures solubilized in detergent and/or reconstituted into lipid bilayers, thus providing unprecedented insight into the mechanisms underlying ion channel–lipid interactions. Here, we describe how ion channel structures have evolved to respond to both lipid modulators and lipid activators to control the electrical activities of cells, highlighting diverse mechanisms and common themes. Ion channel structures reveal mechanisms of lipid action, including how channel gating is altered by direct binding of signaling lipids and those within the membrane itself, as well as mechanical and architectural effects of membrane lipids.