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.
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.
The identification of four acidic amino acids as potential calcium-binding residues in the TMEM16A calcium-activated chloride channel furthers the molecular understanding of this ion channel family.
Structures of the non-canonical potassium channel TMEM175 in open and closed states reveal unique mechanisms for channel gating and the selective permeation of K+ ions.
The structural relationship between TMC and TMEM16 proteins provides insight into the structure and functional mechanisms of the mechanotransduction channel complex in hair cells.
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.
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.
SOM+ GABAergic neuronal signaling and inhibitory transmission in the central lateral amygdala is regulated by TMEM16B, which is also involved in fear and anxiety-like behaviors.
