title: Force generation, work, and coupling in molecular motors.
abstract: A mechanism is proposed for molecular motors in which force is generated by a protein conformational change driven by binding energy (in muscle, that of myosin with actin as well as with ATP, ADP, or Pi). Work, the product of the force generated by one myosin or kinesin molecule (F) and the distance over which it acts (d), is a function of a ratio of dissociation constants before and after the contractile step: F.d < RT ln(KAe/KAc). From published data the ratio is > 2 x 10(4), which can be explained by conversion of a surface complex to an enclosed, or partly enclosed, complex. Although the complex performing the work stroke is in unstrained conformation, the complex after the work stroke is much more stable, owing to binding forces; the latter, however, is destabilized by the load, which thereby opposes the contractile conformational change, countering the force-generating reaction. The connection between the free energy release and work is implicit in the mechanism, inasmuch as coupling, like force generation, depends on conformational changes driven by binding energy (internal rather than external work being involved in coupling). The principles apply whether ATP or an ion gradient drives the system. At high load, in muscle, the mechanism allows for a summation of the forces generated by several myosin molecules.
authors.affiliation: Pest Management Research Centre, London, Ontario, Canada.
authors.forename: R M
authors.initials: RM
authors.lastname: Krupka
mesh_terms: D000199:Actins / Q000737:chemistry / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D004734:Energy Metabolism; D066298:In Vitro Techniques; D016547:Kinesins / Q000737:chemistry / Q000502:physiology; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009218:Myosins / Q000737:chemistry / Q000502:physiology; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D000199:Actins; D000255:Adenosine Triphosphate; D009218:Myosins; D016547:Kinesins