Sarcomere Lattice Geometry Influences Cooperative Myosin Binding in Muscle
Figure 3
Model kinetic structure (using the same color scheme as Figure 1) shows coupled, three-state cycles for thin-filament activation and cross-bridge formation. Thin-filament states TF1, TF2, and TF3, represent no Ca2+ bound to troponin, Ca2+ bound to troponin, and Ca2+ bound to troponin plus a movement of tropomyosin that exposes myosin binding sites on actin, respectively. TF1 and TF2 represent thin-filament conformations where myosin cannot bind to actin. Cross-bridge states XB1, XB2, and XB3 represent unbound, bound pre-powerstroke, and bound post-powerstroke actomyosin conformations, respectively. Cross-bridge conformations associated with XB2 and XB3 bear force. We list a possible biochemical condition associated with each cross-bridge state using A, M, D, and P to represent actin, myosin, ADP, and inorganic phosphate (Pi). A ∼ M signifies the unbound state (XB1), and A . M represents actomyosin binding (XB2 and XB3). While transition rates between cross-bridge states (rx,ij) depend on position and cross-bridge distortion, the transition rates between thin-filament states (rt,ij) do not. Note that the transition between XB3 and XB1 is biochemically associated with a release of ADP, myosin binding another ATP, dissociation of myosin from actin, and hydrolysis of ATP into products ADP and Pi. Thin-filament transitions from TF3 to TF2 are not permitted while a cross-bridge is bound. Each cycle is thermodynamically balanced (Equations 7 and 14).