Cross-bridge action: present views, prospects, and unknowns

When the sliding filament hypothesis was proposed in 1953-1954, existing ev idence showed that (1) contributions to tension were given by active sites uniformly distributed within each zone of filament overlap and (2) each sit e functioned cyclically. These sites were identified by electron microscopy as cross-bridges between the two filaments, formed of the heads of myosin molecules projecting from a thick filament and attaching to a thin filament . The angle of these cross-bridges was found to be different at rest and in rigor, suggesting that the event causing relative motion of the filaments was a change of the angle of the cross-bridges. At first, it seemed likely that the whole cross-bridge rotated about its attachment to actin, but when the atomic structures of actin and myosin were obtained by X-ray crystallo graphy, a possible hinge was found between the "catalytic domain" which att aches to the actin filament and the "light-chain domain" which appears to a ct as a lever arm. Two attitudes of the lever arm are now well established, the transition between them being driven by a conformational change couple d to some step in the hydrolysis of ATP, but several recent observations su ggest that this is not the whole story: a third attitude has been shown by X-ray crystallography; a non-muscle myosin has been shown to produce its wo rking stroke in two steps; and there are suggestions that an additional dis placement of the filaments is produced by a change in the attitude of the c atalytic domain on the thin filament. (C) 2000 Published by Elsevier Scienc e Ltd.