Cardiac V1 and V3 myosins differ in their hydrolytic and mechanical activities in vitro.

The two mammalian cardiac myosin heavy chain isoforms, alpha and beta, have 93% amino acid homology, but hearts expressing these myosins exhibit marked differences in their mechanical activities. To further understand the function of these cardiac myosins as molecular motors, we compared the ability of these myosins to hydrolyze ATP and to both translocate actin filaments and generate force in an in vitro motility assay. V1 myosin has twice the actin-activated ATPase activity and three times the actin filament sliding velocity when compared with V3 myosin. In contrast, the force-generating ability of these myosins is quite different when the total force produced by a small population of myosin molecules (> 50) is examined. V1 myosin produces only one half the average cross-bridge force of V3 myosin. With discrete areas of primary structural heterogeneity known to exist between alpha and beta heavy chains, the differences we report in the hydrolytic and mechanical activities of the motors are explored in the context of potential structural and kinetic differences between the V1 and V3 myosins.