Diagrammatic version of the three-state model as originally envisaged by McKillop and Geeves (1993) . Tpm on a single strand of seven actin monomers can sit in one of three positions on the actin surface B, C, or O. In the B position, the major binding sites of myosin on actin are blocked by Tpm, and no significant binding of myosin is possible (weak electrostatic interaction may be possible). In the C position, myosin can bind to some of its binding site to form the relatively weakly Attached or A state, but rotation into the rigor-like state (R) is prevented by Tpm. More recent structural interpretations of the transition from A to R state would suggest that the A state is formed by the lower 50 kD domain of myosin binding to actin. The R state requires closure of the cleft between the upper and lower 50 kD domains (linked to switch one opening), allowing the upper 50 kD to access its binding site on actin. In the C state of the thin filament, the position of Tpm would sit between the upper and lower 50 kD domains forming a molecular gag preventing cleft closure. See Table 1 for the occupancy of the different states under different conditions. The term Ki refers to the equilibrium constants for each step of the scheme defined in the left to right or top down direction.
