Single cardiac ventricular myosins are autonomous motors
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 ex...
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doaj-ceb5d5e493df461bba2ab23d2e9ad2892020-11-25T03:59:37ZengThe Royal SocietyOpen Biology2046-24412018-04-018410.1098/rsob.170240170240Single cardiac ventricular myosins are autonomous motorsYihua WangChen-Ching YuanKatarzyna KazmierczakDanuta Szczesna-CordaryThomas P. BurghardtMyosin 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.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170240single cardiac myosin mechanicssuper-resolution microscopyratcheting myosin essential light chainqdot labelled actin under loadcardiomyopathy-linked mutants |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yihua Wang Chen-Ching Yuan Katarzyna Kazmierczak Danuta Szczesna-Cordary Thomas P. Burghardt |
spellingShingle |
Yihua Wang Chen-Ching Yuan Katarzyna Kazmierczak Danuta Szczesna-Cordary Thomas P. Burghardt Single cardiac ventricular myosins are autonomous motors Open Biology single cardiac myosin mechanics super-resolution microscopy ratcheting myosin essential light chain qdot labelled actin under load cardiomyopathy-linked mutants |
author_facet |
Yihua Wang Chen-Ching Yuan Katarzyna Kazmierczak Danuta Szczesna-Cordary Thomas P. Burghardt |
author_sort |
Yihua Wang |
title |
Single cardiac ventricular myosins are autonomous motors |
title_short |
Single cardiac ventricular myosins are autonomous motors |
title_full |
Single cardiac ventricular myosins are autonomous motors |
title_fullStr |
Single cardiac ventricular myosins are autonomous motors |
title_full_unstemmed |
Single cardiac ventricular myosins are autonomous motors |
title_sort |
single cardiac ventricular myosins are autonomous motors |
publisher |
The Royal Society |
series |
Open Biology |
issn |
2046-2441 |
publishDate |
2018-04-01 |
description |
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. |
topic |
single cardiac myosin mechanics super-resolution microscopy ratcheting myosin essential light chain qdot labelled actin under load cardiomyopathy-linked mutants |
url |
https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170240 |
work_keys_str_mv |
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