Physical principles underlying the transduction of bilayer deformation forces during mechanosensitive channel gating.
In mechanosensitive (MS) channels, gating is initiated by changes in intra-bilayer pressure profiles originating from bilayer deformation. Here we evaluated two physical mechanisms as triggers of MS channel gating: the energetic cost of protein-bilayer hydrophobic mismatches and the geometric consequences of bilayer intrinsic curvature. Structural changes in the Escherichia coli large MS channel (MscL) were studied under nominally zero transbilayer pressures using both patch clamp and EPR spectroscopic approaches. Changes in membrane intrinsic curvature induced by the external addition of lysophosphatidylcholine (LPC) generated massive spectroscopic changes in the narrow constriction that forms the channel 'gate', trapping the channel in the fully open state. Hydrophobic mismatch alone was unable to open the channel, but decreasing bilayer thickness lowered MscL activation energy, stabilizing a structurally distinct closed channel intermediate. We propose that the mechanism of mechanotransduction in MS channels is defined by both local and global asymmetries in the transbilayer pressure profile at the lipid-protein interface.
Perozo
Eduardo
E
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22906, USA. eperozo@virginia.edu
Kloda
Anna
A
Cortes
D Marien
DM
Martinac
Boris
B
D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D008051:Lipid Bilayers; D018408:Patch-Clamp Techniques
D029968:Escherichia coli Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; C086596:MscL protein, E coli