Structural basis of closed groove scrambling by a TMEM16 protein.

ABSTRACT: Activation of Ca²⁺-dependent TMEM16 scramblases induces phosphatidylserine externalization, a key step in multiple signaling processes. Current models suggest that the TMEM16s scramble lipids by deforming the membrane near a hydrophilic groove and that Ca²⁺ dependence arises from the different association of lipids with an open or closed groove. However, the molecular rearrangements underlying groove opening and how lipids reorganize outside the closed groove remain unknown. Here we directly visualize how lipids associate at the closed groove of Ca²⁺-bound fungal nhTMEM16 in nanodiscs using cryo-EM. Functional experiments pinpoint lipid-protein interaction sites critical for closed groove scrambling. Structural and functional analyses suggest groove opening

SUBMITTER: Feng Z 

PROVIDER: S-EPMC12801940 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature