Cross-bridge movement in muscle and the conformation of the myosin hinge.

The force-generating mechanism in muscle is discussed and it is shown that a helix-coil transition in the S-2 link of the cycling cross-bridge is compatible with the physical and chemical properties of this region of the myosin molecule. Thermal melting and temperature-jump experiments are described demonstrating that the light meromyosin-heavy meromyosin (LMM-HMM) hinge domain of S-2 is a segment of low thermal stability. This region can undergo alpha-helix-random coil transitions on a time-scale comparable to the quick-recovery tension transient observed when isometrically contracting muscle is abruptly shortened or stretched. Cross-linking and enzyme probe studies of glycerinated muscle fibres and myofibrils in resting, rigor and activating solvents suggest that the polypeptide chains within the hinge region of S-2 undergo a conformational transition to a more open, proteolytically sensitive structure when the S-2 link is released from the thick filament surface.