Single cardiac ventricular myosins are autonomous motors

Yihua Wang, Chen Ching Yuan, Katarzyna Kazmierczak, Danuta Szczesna-Cordary, Thomas P Burghardt

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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 a-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.

Original languageEnglish (US)
Article number170240
JournalOpen Biology
Volume4
Issue number8
DOIs
StatePublished - Jan 1 2018

Keywords

  • Cardiomyopathy-linked mutants
  • Qdot labelled actin under load
  • Ratcheting myosin essential light chain
  • Single cardiac myosin mechanics
  • Super-resolution microscopy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Wang, Y., Yuan, C. C., Kazmierczak, K., Szczesna-Cordary, D., & Burghardt, T. P. (2018). Single cardiac ventricular myosins are autonomous motors. Open Biology, 4(8), [170240]. https://doi.org/10.1098/rsob.170240