Diverse roles of lipids in ion conduction by TMEM16 lipid scramblases

Abstract

Lipid scramblases from the TMEM16 protein family facilitate passive lipid transport between membrane leaflets but also operate as ion channels, with implication in diverse physiological processes such as cell volume regulation and apoptosis. Such dual functionality implies tight coupling between lipid and ion transport mediated by the scramblases. Here we used extensive atomistic molecular dynamics simulations and the computational electrophysiology method to study molecular mechanisms of ion conduction in fungal nhTMEM16 and human TMEM16K lipid scramblases with a particular focus on the roles that lipids play in ion permeability and selectivity.