Mechanosensitive channels in bacteria as membrane tension reporters.
The purpose of this short review is to discuss recent data on the molecular structure and mechanism of gating of MscL, a mechanosensitive channel of large conductance from Escherichia coli. MscL is the first isolated molecule shown to convert mechanical stress of the membrane into a simple response, the opening of a large aqueous pore. The functional complex appears to be a stable homo-pentamer of 15-kDa subunits, the gating transitions in which are driven by stretch forces conveyed through the lipid bilayer. We have measured the open probability of MscL and the kinetics of transitions as a function of membrane tension. The parameters extracted from the single-channel current recordings and dose-response curves such as the energy difference between the closed, open, and intermediate conducting states, and the transition-related changes in protein dimensions suggest a large conformational rearrangement of the channel complex. The estimations show that in native conditions MscL openings could be driven primarily by forces of osmotic nature. The thermodynamic and spatial parameters reasonably correlate with the available data on the structure of a single MscL subunit and multimeric organization of the complex. Combined with the functional analysis of mutations, these data give grounds to hypotheses on the nature of the channel mechanosensitivity.
Sukharev
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Department of Biology, University of Maryland, College Park, Maryland 20742, USA. ss311@umail.umd.edu
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology*; D004926:Escherichia coli / Q000737:chemistry; D029968:Escherichia coli Proteins; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D007473:Ion Channels; C086596:MscL protein, E coli