The ATPase cycle of human muscle myosin II Isoforms: adaptation of a single mechanochemical cycle for different physiological roles

Striated muscle myosins are encoded by a large gene family in all mammals, including human. These isoforms define several of the key characteristics of the different striated muscle fiber types including maximum shortening velocity. We have previously used recombinant isoforms of the motor domains of seven different human myosin isoforms to define the actin.myosin cross-bridge cycle in solution. Here we present data on an eighth isoform the perinatal, which has not previously been charaterized. The perinatal is distinct from the embryonic isoforms appearing to have features in common with the adult fast muscle isoform, including weak affinity of ADP for A.M and fast ADP release. We go on to use a recently developed modeling approach MUSICO to explore how well the experimentally defined cross-bridge cycles for each isoform in solution can predict the characteristics of muscle fiber contraction including duty ratio, shortening velocity, ATP economy and the load dependence of these parameters. The work shows that the parameters of the cross bridge cycle predict many of the major characteristics of each muscle fiber type and raises the question of what sequence changes are responsible for these characteristics.