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Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and Pi Release

  • The actomyosin system generates mechanical work with the execution of the power stroke, an ATP-driven, two-step rotational swing of the myosin-neck that occurs post ATP hydrolysis during the transition from weakly to strongly actin-bound myosin states concomitant with Pi release and prior to ADP dissociation. The activating role of actin on product release and force generation is well documented; however, the communication paths associated with weak-to-strong transitions are poorly characterized. With the aid of mutant analyses based on kinetic investigations and simulations, we identified the W-helix as an important hub coupling the structural changes of switch elements during ATP hydrolysis to temporally controlled interactions with actin that are passed to the central transducer and converter. Disturbing the W-helix/transducer pathway increased actin-activated ATP turnover and reduced motor performance as a consequence of prolonged duration of the strongly actin-attached states. Actin-triggered Pi release was accelerated, while ADP release considerably decelerated, both limiting maximum ATPase, thus transforming myosin-2 into a high-duty-ratio motor. This kinetic signature of the mutant allowed us to define the fractional occupancies of intermediate states during the ATPase cycle providing evidence that myosin populates a cleft-closure state of strong actin interaction during the weak-to-strong transition with bound hydrolysis products before accomplishing the power stroke.

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Document Type:Article
Author:Peter Franz, Wiebke Ewert, Matthias Preller, Georgios Tsiavaliaris
Parent Title (English):International Journal of Molecular Sciences
Article Number:104
Number of pages:19
Place of publication:Basel
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2020/12/24
Copyright:© 2020 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Funding Information:This research work was funded by the Deutsche Forschungsgemeinschaft (DFG), grant numbers PR1478/2-1 (M.P.) and TS169/5-1 (G.T.).
Keyword:ATPase cycle; actin; allosteric communication; duty ratio; force generation; myosin; power stroke; transient kinetics
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Institut für Technik, Ressourcenschonung und Energieeffizienz (TREE)
Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Entry in this database:2021/01/06
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International