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Article

Structural and Computational Insights into a Blebbistatin-Bound Myosin•ADP Complex with Characteristics of an ADP-Release Conformation along the Two-Step Myosin Power Stoke

1
Institute for Biophysical Chemistry, Structural Bioinformatics and Chemical Biology, Hannover Medical School, 30625 Hannover, Germany
2
Institute for Biophysical Chemistry, Cellular Biophysics, Hannover Medical School, 30625 Hannover, Germany
3
Department of Natural Sciences, University of Applied Sciences Bonn-Rhein-Sieg, 53359 Rheinbach, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(19), 7417; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197417
Received: 28 September 2020 / Accepted: 6 October 2020 / Published: 8 October 2020
(This article belongs to the Section Molecular Biophysics)
The motor protein myosin drives a wide range of cellular and muscular functions by generating directed movement and force, fueled through adenosine triphosphate (ATP) hydrolysis. Release of the hydrolysis product adenosine diphosphate (ADP) is a fundamental and regulatory process during force production. However, details about the molecular mechanism accompanying ADP release are scarce due to the lack of representative structures. Here we solved a novel blebbistatin-bound myosin conformation with critical structural elements in positions between the myosin pre-power stroke and rigor states. ADP in this structure is repositioned towards the surface by the phosphate-sensing P-loop, and stabilized in a partially unbound conformation via a salt-bridge between Arg131 and Glu187. A 5 Å rotation separates the mechanical converter in this conformation from the rigor position. The crystallized myosin structure thus resembles a conformation towards the end of the two-step power stroke, associated with ADP release. Computationally reconstructing ADP release from myosin by means of molecular dynamics simulations further supported the existence of an equivalent conformation along the power stroke that shows the same major characteristics in the myosin motor domain as the resolved blebbistatin-bound myosin-II·ADP crystal structure, and identified a communication hub centered on Arg232 that mediates chemomechanical energy transduction. View Full-Text
Keywords: myosin; molecular motor; ADP release; blebbistatin; structural biology; cytoskeleton; molecular dynamics simulations; force generation myosin; molecular motor; ADP release; blebbistatin; structural biology; cytoskeleton; molecular dynamics simulations; force generation
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MDPI and ACS Style

Ewert, W.; Franz, P.; Tsiavaliaris, G.; Preller, M. Structural and Computational Insights into a Blebbistatin-Bound Myosin•ADP Complex with Characteristics of an ADP-Release Conformation along the Two-Step Myosin Power Stoke. Int. J. Mol. Sci. 2020, 21, 7417. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197417

AMA Style

Ewert W, Franz P, Tsiavaliaris G, Preller M. Structural and Computational Insights into a Blebbistatin-Bound Myosin•ADP Complex with Characteristics of an ADP-Release Conformation along the Two-Step Myosin Power Stoke. International Journal of Molecular Sciences. 2020; 21(19):7417. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197417

Chicago/Turabian Style

Ewert, Wiebke, Peter Franz, Georgios Tsiavaliaris, and Matthias Preller. 2020. "Structural and Computational Insights into a Blebbistatin-Bound Myosin•ADP Complex with Characteristics of an ADP-Release Conformation along the Two-Step Myosin Power Stoke" International Journal of Molecular Sciences 21, no. 19: 7417. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197417

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