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.
cryo-EM reveals the properties of distinct conformations occupied during activation of the lipid scramblase nhTMEM16 and provides new insights into its interactions with the lipid environment.
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.
The structural relationship between TMC and TMEM16 proteins provides insight into the structure and functional mechanisms of the mechanotransduction channel complex in hair cells.
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.
The amino acids that are necessary for phospholipid scrambling by ANO6/TMEM16F can, via domain swapping, confer scrambling activity to the chloride ion channel ANO1 that normally does not scramble phospholipids.
LRRC8A is an essential component of a mechanoresponsive ion channel signaling complex that tunes skeletal muscle differentiation, muscle cell size, function and metabolic pathways to regulate adiposity and systemic glycemia.
