Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F.

The lipid scramblase TMEM16F initiates blood coagulation by catalyzing the exposure of phosphatidylserine in platelets. The protein is part of a family of membrane proteins, which encompasses calcium-activated channels for ions and lipids. Here, we reveal features of murine TMEM16F (mTMEM16F) that underlie its function as a lipid scramblase and an ion channel.

Independent activation of ion conduction pores in the double-barreled calcium-activated chloride channel TMEM16A.

The TMEM16 proteins constitute a family of membrane proteins with unusual functional breadth, including lipid scramblases and Cl channels. Members of both these branches are activated by Ca, acting from the intracellular side, and probably share a common architecture, which was defined in the recent structure of the lipid scramblase nhTMEM16. The structural features of subunits and the arrangement of Ca-binding sites in nhTMEM16 suggest that the dimeric protein harbors two locations for catalysis that are independent with respect to both activation and lipid conduction.

X-ray structure of a calcium-activated TMEM16 lipid scramblase.

The TMEM16 family of proteins, also known as anoctamins, features a remarkable functional diversity. This family contains the long sought-after Ca(2+)-activated chloride channels as well as lipid scramblases and cation channels. Here we present the crystal structure of a TMEM16 family member from the fungus Nectria haematococca that operates as a Ca(2+)-activated lipid scramblase.