Authors
Taoran Xiao, Alexandra Kovinko, Chaowei Shi, Henry Sawczyc, Denis Qoraj, Carl Öster, Thiemo Sprink, Anton F Ketzel, Sascha Lange, Spyridon Kosteletos, Han Sun, Daniel Roderer, Shanshuang Chen, Adam Lange
Published in
Science advances. Volume 12. Issue 41. Pages eaei0096. Oct 09, 2026. Epub Oct 07, 2026.
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.
PMID:
42842685
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.
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