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

ABSTRACT: 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. The cryo-EM data of mTMEM16F in absence and presence of Ca²⁺ define the ligand-free closed conformation of the protein and the structure of a Ca²⁺-bound intermediate. Both conformations resemble their counterparts of the scrambling-incompetent anion channel mTMEM16A, yet with distinct differences in the region of ion and lipid permeation. In conjunction with functional data, we demonstrate the relationship betwe

SUBMITTER: Alvadia C 

PROVIDER: S-EPMC6414204 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature