APPS November 2002 Meeting Abstract 337

Mechanosensitive (MS) ion channels have been documented in cells belonging to prokaryotic and eukaryotic organisms¹. The channels act as mechano-electrical switches, which open in response to cell membrane deformations. This process is critical to the response of living organisms to direct physical stimulation, as in hearing, touch or osmoregulation. In prokaryotes MS channels were first documented in bacteria. Among MS channels studied to date, the best characterized is MscL, the bacterial MS channel of large conductance, which has become a prototype MS channel to study structure-function relationship in this class of ion channels. The 3D structure of MscL was determined by X-ray crystallography showing that the MscL channel is a homopentamer². To probe the molecular mechanism of how mechanical force gates MscL we have recently evaluated two physical mechanisms as triggers of MscL gating by membrane deformation forces: (i) the energetic cost of protein-lipid bilayer hydrophobic mismatches and (ii) the geometric consequences of bilayer intrinsic curvature. Structural changes in MscL from E. coli were studied using EPR spectroscopy and site-directed spin labeling, whereas the channel function was examined by the patch clamp technique³. We have determined the structural rearrangements that underlie MscL closed to open transitions. The open state is highly dynamic, supporting a water-filled pore of at least 25 Å in diameter⁴ in agreement with the single-channel permeation studies, which indicated MscL pore of ∼30 Å¹. Our studies suggest a plausible molecular mechanism of gating in mechanosensitive channels.