Single cardiac ventricular myosins are autonomous motors

• Published in: Open biology 2018-04, Vol.8 (4), p.170240
• Main Authors: Wang, Yihua, Yuan, Chen-Ching, Kazmierczak, Katarzyna, Szczesna-Cordary, Danuta, Burghardt, Thomas P.
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - metabolism; Actin Cytoskeleton - physiology; Animals; Cardiac Myosins - chemistry; Cardiac Myosins - genetics; Cardiac Myosins - physiology; Cardiomyopathy-Linked Mutants; Humans; Mice; Mice, Transgenic; Models, Molecular; Myosin Light Chains - chemistry; Myosin Light Chains - genetics; Qdot Labelled Actin Under Load; Ratcheting Myosin Essential Light Chain; Single Cardiac Myosin Mechanics; Super-Resolution Microscopy; Ventricular Myosins - chemistry; Ventricular Myosins - genetics; Ventricular Myosins - physiology
• ISSN: 2046-2441; 2046-2441
• DOI: 10.1098/rsob.170240

Myosin transduces ATP free energy into mechanical work in muscle. Cardiac muscle has dynamically wide-ranging power demands on the motor as the muscle changes modes in a heartbeat from relaxation, via auxotonic shortening, to isometric contraction. The cardiac power output modulation mechanism is explored in vitro by assessing single cardiac myosin step-size selection versus load. Transgenic mice express human ventricular essential light chain (ELC) in wild- type (WT), or hypertrophic cardiomyopathy-linked mutant forms, A57G or E143K, in a background of mouse α-cardiac myosin heavy chain. Ensemble motility and single myosin mechanical characteristics are consistent with an A57G that impairs ELC N-terminus actin binding and an E143K that impairs lever-arm stability, while both species down-shift average step-size with increasing load. Cardiac myosin in vivo down-shifts velocity/force ratio with increasing load by changed unitary step-size selections. Here, the loaded in vitro single myosin assay indicates quantitative complementarity with the in vivo mechanism. Both have two embedded regulatory transitions, one inhibiting ADP release and a second novel mechanism inhibiting actin detachment via strain on the actin-bound ELC N-terminus. Competing regulators filter unitary step-size selection to control force-velocity modulation without myosin integration into muscle. Cardiac myosin is muscle in a molecule.