While activated by a common mechanism, both functions in TMEM16F - lipid scrambling and ion conduction - are likely mediated by alternate protein conformations that are at equilibrium in the ligand-bound state.
Structures of a TMEM16 phospholipid scramblase reveal that its Ca2+-dependent activation entails global conformational changes and how these rearrangements affect the membrane to enable transbilayer lipid transfer.
A concerted approach employing equilibrium and biased molecular simulations, electrophysiology, mutagenesis, and functional assays reveals, in atomic details, the mechanism and pathway for transport of phospholipids and ions by a lipid scramblase.
Single-particle cryo-EM and electrophysiology studies of the chloride channel TMEM16A reveals the structural basis for anion conduction and uncover its relationship to lipid scramblases of the same family.
Ion conduction in the calcium-activated chloride channel TMEM16A is directly regulated by calcium, which binds to a site close to the pore thereby shaping the electrostatics at its intracellular entrance.