Molecular mechanics of mouse cardiac myosin isoforms

Abstract

Two myosin isoforms are expressed in myocardium, αα-homodimers (V1) and ββ-homodimers (V3). V1exhibits higher velocities and myofibrillar ATPase activities compared with V3. We also observed this for cardiac myosin from normal (V1) and propylthiouracil-treated (V3) mice. Actin velocity in a motility assay ( V actin) over V1 myosin was twice that of V3 as was the myofibrillar ATPase. Myosin's average force (Favg) was similar for V1 and V3. Comparing V actin and Favg across species for both V1 and V3, our laboratory showed previously (VanBuren P, Harris DE, Alpert NR, and Warshaw DM. Circ Res 77: 439–444, 1995) that mouse V1 has greater V actin and Favg compared with rabbit V1. Mouse V3 V actin was twice that of rabbit V actin. To understand myosin's molecular structure and function, we compared α- and β-cardiac myosin sequences from rodents and rabbits. The rabbit α- and β-cardiac myosin differed by eight and four amino acids, respectively, compared with rodents. These residues are localized to both the motor domain and the rod. These differences in sequence and mechanical performance may be an evolutionary attempt to match a myosin's mechanical behavior to the heart's power requirements.