title: Functional implications of the two-headed structure of myosin.
abstract: This review summarizes the results obtained by biochemical and physiological studies on the functional implications of the two-headed structure of the myosin molecule. Our nonidentical two-head hypothesis of myosin is supported by biochemical studies on myosin ATPase. The reaction mechanism of the Mg2+-ATPase reaction catalyzed by one head of the myosin molecule is shown to be different from that catalyzed by the other head, and the reaction intermediate, MPADP, is produced in head B but not in head A. Evidence for differences in the chemical structures of the two heads of myosin is also presented. The myosin preparation is shown to be a mixture of homodimers with respect to its g-chain composition, but every homodimer has the non-identical two heads, B and A. Furthermore, the molecular mechanism for acceleration of the Mg2+-ATPase reaction by F-actin and that for its control by Ca2+ ions and Mg2+-ATP are discussed, based on the nonidentical two-head hypothesis of the myosin molecule. It was shown that the formation and decomposition of the key intermediate, A(B)MPADP are required for tension development and shortening. One cycle of ATP hydrolysis by crossbridges synchronously initiated by a rapid stretch or a sudden release of a slow stretch, indicating that the probability of dissociation of a crossbridge by its interaction with ATP depends on its angular position. It is also demonstrated that rotation of the base of nucleoside triphosphate about the glycosyl bond is essential for formation of MPXDP from M2XTP, as well as for muscle contraction. Based on these biochemical and physiological studies on the movement of the myosin head in muscle contraction, a molecular mechanism for muscle contraction is proposed.
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000244:Adenosine Diphosphate; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002413:Cations, Divalent; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D009119:Muscle Contraction; D009132:Muscles / Q000201:enzymology / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D002413:Cations, Divalent; D007527:Isoenzymes; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000205:Actomyosin; D000251:Adenosine Triphosphatases; D009218:Myosins; D000252:Calcium-Transporting ATPases