Structural basis of closed groove scrambling by a TMEM16 protein.

ABSTRACT: Activation of Ca²⁺-dependent TMEM16 scramblases induces the externalization of phosphatidylserine, a key molecule 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 involved in groove opening and of how lipids reorganize outside the closed groove remain unknown. Using cryogenic electron microscopy, we directly visualize how lipids associate at the closed groove of Ca²⁺-bound nhTMEM16 in nanodiscs. Functional experiments pinpoint the lipid-protein interaction sites critical for closed groove scrambling. Structural and functional

SUBMITTER: Feng Z 

PROVIDER: S-EPMC10441378 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature