In our recent article published in Nature Communications entitled: “Structural basis of the gating mechanism of the large-conductance mechanosensitive channel from Escherichia coli“ we solved two structures of the mechanosensitive chanel of large conductance MscL from E. coli, by cryoEM in the closed conformation in DMPC and DOPC lipid nanodiscs. EcMscL was the first mechanosensitive channel discovered and subsequently served as a model system for understanding mechanical sensing, becoming one of the most decorated and well-studied systems Using PELDOR/DEER spectroscopy, we screened for conditions and identified that in DSPC lipids, the EcMscL conformational ensemble shifts away from the closed state and that open-like states are present. We then solved the structure in an expanded state by cryoEM, revealing an architecture with pore properties consistent with previous electrophysiology reports. By further combining hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations, we investigated the dynamics of EcMscL gating in lipid bilayers, identifying sites involved in the closed-to-expanded transition. Combined, this enables us to inform on the elusive structural mechanism of EcMscL mechanosensitive channel function.. More information could be found here.
