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

7 Citations (Scopus)

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

Fingerprint

Cardiac Myosins
Ventricular Myosins
Myosins
Muscle
Actins
Light
Muscles
Isometric Contraction
Modulation
Myosin Heavy Chains
Hypertrophic Cardiomyopathy
Cardiac Output
Adenosine Diphosphate
Transgenic Mice
Force control
Myocardium
Adenosine Triphosphate
Free energy
Assays
Molecules

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)

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

Single cardiac ventricular myosins are autonomous motors. / Wang, Yihua; Yuan, Chen Ching; Kazmierczak, Katarzyna; Szczesna-Cordary, Danuta; Burghardt, Thomas P.

In: Open Biology, Vol. 4, No. 8, 170240, 01.01.2018.

Research output: Contribution to journalArticle

Wang, Y, Yuan, CC, Kazmierczak, K, Szczesna-Cordary, D & Burghardt, TP 2018, 'Single cardiac ventricular myosins are autonomous motors', Open Biology, vol. 4, no. 8, 170240. https://doi.org/10.1098/rsob.170240
Wang Y, Yuan CC, Kazmierczak K, Szczesna-Cordary D, Burghardt TP. Single cardiac ventricular myosins are autonomous motors. Open Biology. 2018 Jan 1;4(8). 170240. https://doi.org/10.1098/rsob.170240
Wang, Yihua ; Yuan, Chen Ching ; Kazmierczak, Katarzyna ; Szczesna-Cordary, Danuta ; Burghardt, Thomas P. / Single cardiac ventricular myosins are autonomous motors. In: Open Biology. 2018 ; Vol. 4, No. 8.
@article{4cb9bb6f937344deae6fe128fe1cdfc7,
title = "Single cardiac ventricular myosins are autonomous motors",
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.",
keywords = "Cardiomyopathy-linked mutants, Qdot labelled actin under load, Ratcheting myosin essential light chain, Single cardiac myosin mechanics, Super-resolution microscopy",
author = "Yihua Wang and Yuan, {Chen Ching} and Katarzyna Kazmierczak and Danuta Szczesna-Cordary and Burghardt, {Thomas P}",
year = "2018",
month = "1",
day = "1",
doi = "10.1098/rsob.170240",
language = "English (US)",
volume = "4",
journal = "Open Biology",
issn = "2046-2441",
publisher = "Royal Society Publishing",
number = "8",

}

TY - JOUR

T1 - Single cardiac ventricular myosins are autonomous motors

AU - Wang, Yihua

AU - Yuan, Chen Ching

AU - Kazmierczak, Katarzyna

AU - Szczesna-Cordary, Danuta

AU - Burghardt, Thomas P

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Cardiomyopathy-linked mutants

KW - Qdot labelled actin under load

KW - Ratcheting myosin essential light chain

KW - Single cardiac myosin mechanics

KW - Super-resolution microscopy

UR - http://www.scopus.com/inward/record.url?scp=85045548927&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045548927&partnerID=8YFLogxK

U2 - 10.1098/rsob.170240

DO - 10.1098/rsob.170240

M3 - Article

VL - 4

JO - Open Biology

JF - Open Biology

SN - 2046-2441

IS - 8

M1 - 170240

ER -