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

• Published in: The Journal of biological chemistry 2019-09, Vol.294 (39), p.14267-14278
• Main Authors: Johnson, Chloe A., Walklate, Jonathan, Svicevic, Marina, Mijailovich, Srboljub M., Vera, Carlos, Karabina, Anastasia, Leinwand, Leslie A., Geeves, Michael A.
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; Adenosine Diphosphate - metabolism; Adenosine Triphosphatases - metabolism; Adenosine Triphosphate - metabolism; adult skeletal myosin; Animals; ATP economy; ATPase; cardiac muscle; cardiac myosin; Cell Line; computer modeling; developmental muscle; developmental myosin; Enzymology; fast muscle; Humans; Mice; Muscle Contraction; Muscles - metabolism; Muscles - physiology; myosin; Myosin Type II - genetics; Myosin Type II - metabolism; Protein Isoforms - genetics; Protein Isoforms - metabolism; skeletal muscle; slow muscle
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.RA119.009825

Striated muscle myosins are encoded by a large gene family in all mammals, including humans. 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 characterized. The perinatal is distinct from the embryonic isoform, appearing to have features in common with the adult fast-muscle isoforms, including weak affinity of ADP for actin·myosin 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 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.