8XW1
Cryo-EM structure of OSCA1.2-V335W-DDM state
Summary for 8XW1
| Entry DOI | 10.2210/pdb8xw1/pdb |
| Related | 8XAJ |
| EMDB information | 38200 38727 |
| Descriptor | Calcium permeable stress-gated cation channel 1 (1 entity in total) |
| Functional Keywords | osca/tmem63 channel, mechanosensitive channel, plant protein |
| Biological source | Arabidopsis thaliana (thale cress) |
| Total number of polymer chains | 1 |
| Total formula weight | 88702.30 |
| Authors | |
| Primary citation | 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, C.D.,Zhang, Y. Mechanical activation opens a lipid-lined pore in OSCA ion channels. Nature, 628:910-918, 2024 Cited by PubMed Abstract: OSCA/TMEM63 channels are the largest known family of mechanosensitive channels, playing critical roles in plant and mammalian 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. PubMed: 38570680DOI: 10.1038/s41586-024-07256-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.49 Å) |
Structure validation
Download full validation report
