Kinetic model of the bacterial large conductance mechanosensitive channel

The recently obtained structural and functional information on the large bacterial mechanosensitive channel MscL allows building a physical model of its gating mechanism. Here we represent MscL as a membrane-embedded elastic rim surrounding the inner gate. Applied membrane tension stretches the rim, and a part of the tension that reaches the gate causes its reversible opening. Physical dimensions and elasticity modules of the rim and inner gate, as well as the energy of gate separation have been assigned and the free energies for the closed and open states were calculated as functions of tension and in-plane area (A) of the channel. The model was fit to the experimental equilibrium distributions of the channel in the two states and to the rate constants for the forward and backward transitions. The computed energy profile for the transition consists of a wider parabola for the closed state and a narrower parabola for the open state. The Young's modulus for the rim in the closed and intermediate states was estimated as 6 MPa, which is 3 times stiffer than that of elastin, while in the open state it was 120 MPa. The estimated energy of gate separation was U = 35 kT. The traveling distance on the reaction coordinate, ΔA, for the expanded-to-open transition is substantially smaller than the entire ΔA_op between the fully closed and open states, which explains previous inconsistency among the experimentally determined ΔA and the physical expansion of the protein predicted by structural models.