From Bench to Biomolecular Simulation: Phospholipid Modulation of Potassium Channels

Abstract

Potassium (K⁺) ion channels are crucial in numerous cellular processes as they hyperpolarise a cell through K⁺ conductance, returning a cell to its resting potential. K⁺ channel mutations result in multiple clinical complications such as arrhythmia, neonatal diabetes and migraines. Since 1995, the regulation of K⁺ channels by phospholipids has been heavily studied using a range of interdisciplinary methods such as cellular electrophysiology, structural biology and computational modelling. As a result, K⁺ channels are model proteins for the analysis of protein-lipid interactions. In this review, we will focus on the roles of lipids in the regulation of K⁺ channels, and how atomic-level structures, along with experimental techniques and molecular simulations, have helped guide our understanding of the importance of phospholipid interactions.

Keywords: Cryo-EM microscopy; K(+) channels; Super-resolution microscopy; X-ray crystallography; electrophysiology; flux assays; mass spectrometry; molecular dynamics simulations; phosphatidylinositol-bisphosphate; phospholipids; protein-lipid interactions.