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| Item Type: | Article |
|---|---|
| Title: | Atomic structure and dynamics of the mechanosensitive channel MscL from Escherichia coli by cryo-EM and solid-state NMR |
| Creators: |
Xiao, Taoran  ORCID: https://orcid.org/0000-0002-9496-6716, Kovinko, Alexandra ORCID: https://orcid.org/0009-0007-3664-0594, Shi, Chaowei ORCID: https://orcid.org/0000-0002-0024-1096, Sawczyc, Henry ORCID: https://orcid.org/0000-0001-9883-0405, Qoraj, Denis ORCID: https://orcid.org/0009-0008-6944-4175, Öster, Carl ORCID: https://orcid.org/0000-0002-8723-4533, Sprink, Thiemo ORCID: https://orcid.org/0000-0002-0760-6828, Ketzel, Anton F. ORCID: https://orcid.org/0009-0001-1741-0650, Lange, Sascha ORCID: https://orcid.org/0009-0003-6941-4981, Kosteletos, Spyridon, Sun, Han ORCID: https://orcid.org/0000-0002-1655-0838, Roderer, Daniel ORCID: https://orcid.org/0000-0002-7276-3467, Chen, Shanshuang ORCID: https://orcid.org/0000-0003-2317-6589 and Lange, Adam ORCID: https://orcid.org/0000-0002-7534-5973
|
| Abstract: | Mechanosensitive channels are central to cellular responses to membrane tension, yet the structural basis of their gating remains incompletely understood. Here, we determine the structures of wild-type and Gly22→Ser (G22S) mutants of MscL from Escherichia coli (EcMscL) by cryogenic electron microscopy (cryo-EM) in peptide-based lipid nanodiscs and complement them with solid-state nuclear magnetic resonance (NMR) measurements in liposomes to capture their dynamics in a native-like membrane environment. The cryo-EM structures reveal a closed conformation, whereas analysis of the low-threshold G22S mutant by NMR uncovers widespread conformational changes in both cytoplasmic and periplasmic regions. These data indicate enhanced dynamics and conformational heterogeneity in the mutant, revealing the early transitions from the closed toward the open state. Together, our results establish a synergistic framework integrating cryo-EM and NMR to resolve both structure and dynamics of mechanosensitive channels, and identify lipid-protein interactions as key determinants of MscL gating and mechanosensitivity. Our study further provides a quantitative benchmark for computational investigations of mechanogating and lays the foundation for the rational design of channels with tunable gating kinetics. |
| Keywords: | Biomolecular Nuclear Magnetic Resonance, Cellular Mechanotransduction, Cryoelectron Microscopy, Escherichia coli, Escherichia coli Proteins, Ion Channels, Liposomes, Magnetic Resonance Spectroscopy, Molecular Models, Mutation, Protein Conformation |
| Source: | Science Advances |
| ISSN: | 2375-2548 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 12 |
| Number: | 41 |
| Page Range: | eaei0096 |
| Date: | 9 October 2026 |
| Official Publication: | https://doi.org/10.1126/sciadv.aei0096 |
| PubMed: | View item in PubMed |
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