EMD-38727

Single-particle
4.49 Å
EMD-38727 Deposition: 15/01/2024
Map released: 10/04/2024
Last modified: 08/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-38727

Cryo-EM structure of OSCA1.2-V335W-DDM state

EMD-38727

Single-particle
4.49 Å
EMD-38727 Deposition: 15/01/2024
Map released: 10/04/2024
Last modified: 08/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Arabidopsis thaliana
Sample: The cryo-EM structure of OSCA1.2-V335W-DDM state
Fitted models: 8xw1 (Avg. Q-score: 0.309)

Deposition Authors: Zhang Y , Han Y
Mechanical activation opens a lipid-lined pore in OSCA ion channels.
Han Y , Zhou Z, Jin R, Dai F, Ge Y, Ju X, Ma X, He S, Yuan L, Wang Y, Yang W , Yue X, Chen Z , Sun Y , Corry B , Cox CD , Zhang Y
(2024) Nature , 628 , 910 - 918
PUBMED: 38570680
DOI: doi:10.1038/s41586-024-07256-9
ISSN: 1476-4687
ASTM: NATUAS
Abstract:
OSCA/TMEM63 channels are the largest known family of mechanosensitive channels1-3, playing critical roles in plant4-7 and mammalian8,9 mechanotransduction. Here we determined 44 cryogenic electron microscopy structures of OSCA/TMEM63 channels in different environments to investigate the molecular basis of OSCA/TMEM63 channel mechanosensitivity. In nanodiscs, we mimicked increased membrane tension and observed a dilated pore with membrane access in one of the OSCA1.2 subunits. In liposomes, we captured the fully open structure of OSCA1.2 in the inside-in orientation, in which the pore shows a large lateral opening to the membrane. Unusually for ion channels, structural, functional and computational evidence supports the existence of a 'proteo-lipidic pore' in which lipids act as a wall of the ion permeation pathway. In the less tension-sensitive homologue OSCA3.1, we identified an 'interlocking' lipid tightly bound in the central cleft, keeping the channel closed. Mutation of the lipid-coordinating residues induced OSCA3.1 activation, revealing a conserved open conformation of OSCA channels. Our structures provide a global picture of the OSCA channel gating cycle, uncover the importance of bound lipids and show that each subunit can open independently. This expands both our understanding of channel-mediated mechanotransduction and channel pore formation, with important mechanistic implications for the TMEM16 and TMC protein families.