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| Title | Mechanical activation opens a lipid-lined pore in OSCA ion channels. |
|---|---|
| Journal, issue, pages | Nature, Year 2024 |
| Publish date | Apr 3, 2024 |
 Authors | Yaoyao Han / Zijing Zhou / Ruitao Jin / Fei Dai / Yifan Ge / Xisan Ju / Xiaonuo Ma / Sitong He / Ling Yuan / Yingying Wang / Wei Yang / Xiaomin Yue / Zhongwen Chen / Yadong Sun / Ben Corry / Charles D Cox / Yixiao Zhang /   |
| 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 ...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. |
 External links | Nature / PubMed:38570680 |
| Methods | EM (single particle) |
| Resolution | 3.11 - 4.49 Å |
| Structure data | EMDB-38200, PDB-8xaj: EMDB-38503, PDB-8xng: EMDB-38611, PDB-8xry: EMDB-38612, PDB-8xs0: EMDB-38614, PDB-8xs4: EMDB-38615, PDB-8xs5: EMDB-38721, PDB-8xvx: EMDB-38723, PDB-8xvy: EMDB-38724, PDB-8xvz: EMDB-38725, PDB-8xw0: EMDB-38727, PDB-8xw1: EMDB-38728, PDB-8xw2: EMDB-38729, PDB-8xw3: EMDB-38730, PDB-8xw4: |
| Chemicals |  ChemComp-PCW:  ChemComp-P5S: |
| Source |
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 Keywords |  PLANT PROTEIN / OSCA/TMEM63 channel / mechanosensitive channel |
