Mechanosensitive channel gating by delipidation

  title={Mechanosensitive channel gating by delipidation},
  author={Vanessa Judith Flegler and Akiko Rasmussen and Karina Borbil and Lea Boten and Hsuan-Ai Chen and Hanna Deinlein and Julia Halang and Kristin Hellmanzik and Jessica L{\"o}ffler and Vanessa Schmidt and Cihan Makbul and Christian Kraft and Rainer Hedrich and Tim Rasmussen and Bettina B{\"o}ttcher},
  journal={Proceedings of the National Academy of Sciences},
Significance Proteins embedded in membranes experience anisotropic forces from their surroundings. Mechanosensors are activated upon changes in the membrane tension and are the basis of important biological functionalities. However, the molecular mechanisms of mechanosensation are only vaguely understood. Hydrophobic mismatch between protein and membrane, amphiphilic sliding helices, or local membrane bending are examples for different concepts explaining mechanosensation in which one or more… 
Tension mediated mechanical activation and pocket delipidation lead to an analogous MscL state
Whether it is tension or pocket delipidation, MscL samples a similar expanded state, which is the final step of the delipidated pathway but only an intermediate stop of the tension mediated path, hint at synergistic modes of regulation in mechanosensitive channels.
Experimental Investigations on the Conductance of Lipid Membranes under Differential Hydrostatic Pressure
A traditional experimental system consisting of a planar lipid membrane, which is exposed to a controlled, differential hydrostatic pressure, and results indicate a strong correlation between the changes in membrane geometry elicited by the application of pressure, as inferred from capacitance measurements, and the resulting conductance.
Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97
Binding of Triton X 100 is unlikely to mimic structural maturation because mutants with different secretion phenotypes show similar structural responses.


Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS
Cryo-electron microscopy structures of the E. coli small-conductance mechanosensitive channel (MscS) in nanodiscs (ND) reveal a novel membrane-anchoring fold that plays a significant role in channel activation and establish a new location for the lipid bilayer, shifted ~14 Å from previous consensus placements.
Visualization of the mechanosensitive ion channel MscS under membrane tension
Cryo-electron microscopy is used to determine the structure of MscS in different membrane environments, including one that mimics a membrane under tension, and provide a mechanistic underpinning and expand on the ‘force-from-lipids’ model for MSCS mechanosensation.
The role of lipids in mechanosensation
It is proposed that the extent of acyl-chain interdigitation in these pockets determines the conformation of MscS, and it is shown that the volume of the pockets and thus the number of lipid acyl chains within them decreases upon channel opening.
Properties of the Mechanosensitive Channel MscS Pore Revealed by Tryptophan Scanning Mutagenesis
Steady-state fluorescence anisotropy data are consistent with significant homo-Förster resonance energy transfer between tryptophan residues from different subunits within the narrow pore, providing new insights into MscS structure and gating.
Mechanosensitive channels of Escherichia coli: the MscL gene, protein, and activities.
A 2.5-ns mechanosensitive conductance in giant E. coli spheroplasts is discovered and several residues, which when deleted or substituted, affect channel kinetics or mechanosensitivity are identified.
The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels
It is demonstrated that the amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane.
Bacterial Mechanosensitive Channels.
Mechanosensitive (MS) channels protect bacteria against hypo-osmotic shock and fulfil additional functions and a better understanding how MS channels can sense tension on molecular level is developing because the interaction of the lipid bilayer with the channel is being investigated in detail.
The MscS-like channel YnaI has a gating mechanism based on flexible pore helices
It is shown by electron cryomicroscopy that YnaI has an extended sensor paddle that during gating relocates relative to the pore concomitant with bending of a GGxGG motif in the pORE helices, the only one of the six paralogs that has this GGx GG motif allowing the sensor paddle to move outward.