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Updated: Jul 9, 2026
09:38
Dissecting Mechanoenzymatic Properties of Processive Myosins with Ultrafast Force-Clamp Spectroscopy
Published on: July 1, 2021
Mechanoenzymes under superstall and large assisting loads reveal structural features
Denis Tsygankov1, Michael E Fisher
1Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA.
Summary
Motor proteins like kinesin and myosin V exhibit complex velocity changes under varying loads. Their behavior, including backward motion under high loads, is explained by simple kinetic models and free-energy landscapes.
Area of Science:
- Biophysics
- Molecular Biology
- Biochemistry
Background:
- Motor proteins kinesin and myosin V display unusual velocity responses to external forces.
- Kinesin exhibits backward motion under superstall loads and a velocity minimum beyond stall.
- Myosin V shows saturation under assisting loads but rapid backward movement under superstall loads.
Purpose of the Study:
- To understand the origins of complex velocity-force relationships in mechanoenzymes.
- To analyze the role of biochemical kinetics and free-energy landscapes in motor protein function.
- To develop criteria for predicting motor protein behavior under large loads.
Main Methods:
- Analysis of single-molecule experimental data for kinesin and myosin V.
- Application of simple two-state kinetic models.
- Theoretical investigation using free-energy landscape principles.
- Development of criteria for N-state sequential and parallel-pathway models.
Main Results:
- Simple kinetic models accurately predict motor protein behavior at large loads.
- The free-energy landscape, specifically the placement of intermediate mechanochemical states, dictates large-load performance.
- Physical colocalization of distinct biochemical states leads to velocity saturation at large loads.
Conclusions:
- The complex velocity-force profiles of motor proteins arise from their underlying biochemical kinetics and energy landscapes.
- Geometric arrangement of states within the enzymatic cycle is crucial for determining motor protein function under load.
- The findings provide a general framework for understanding mechanoenzyme behavior.
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