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.
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.
The cryo-EM structures of XKR9 define the architecture and caspase-mediated activation of a protein family that is involved in the exposure of phosphatidylserine during apoptosis leading to the engulfment of apoptotic cells by macrophages.
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.
β3-AR signalling via cGMP in cardiomyocytes is regulated via phosphodiesterase 2 and 5 degradation, it is potentially cardioprotective, but dysregulated in heart failure through signal redistribution and higher phosphodiesterase activity.