Cryo-EM Studies of TMEM16F Calcium-Activated Ion Channel Suggest Features Important for Lipid Scrambling.

ABSTRACT: As a Ca²⁺-activated lipid scramblase and ion channel that mediates Ca²⁺ influx, TMEM16F relies on both functions to facilitate extracellular vesicle generation, blood coagulation, and bone formation. How a bona fide ion channel scrambles lipids remains elusive. Our structural analyses revealed the coexistence of an intact channel pore and PIP₂-dependent protein conformation changes leading to membrane distortion. Correlated to the extent of membrane distortion, many tightly bound lipids are slanted. Structure-based mutagenesis studies further reveal that neutralization of some lipid-binding residues or those near membrane distortion specifically alters the onset of lipid scrambling, but not Ca²⁺ influx, thus identifying features outside of channe

SUBMITTER: Feng S 

PROVIDER: S-EPMC6684876 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature