Biophysical Society Thematic Meeting | Tutzing 2026

Single-Molecule FRET: The Next 30 Years

Poster Abstracts

68-POS Board 34 ANALOGIES IN THE CONCERTED MECHANISM OF MYOSIN V AND F1 ATPASE: STRUCTURE, KINETICS AND RATE CONSTANTS Sandor Volkan-Kacso 1,2 ; 1 Azusa Pacific University, Computer Science, Engineering, Mathematics and Physics, Azusa, CA, USA 2 California Institute of Technology, Chemistry and Chemical Engineering, Pasadena, CA, USA A combination of single-molecule experiments -- force spectroscopy, FRET and Cryo-EM -- has recently provided a wealth of new data on the time-resolved function in linear and rotary molecular machines, in particular Myosins and F-ATPases. We propose to treat these data using a mechano-chemical model for Myosin V force generation by exploring the analogy with our previously studied rotary system F1-ATPase. We describe an SN2-like molecular exchange mechanism based on coupled conformational changes from available structural and FRET data. In the model, the binding of mysin to actin occurs in concert with the release of product Pi while concurrently also producing a lever arm swing that drives that forward displacement of the motor along the actin filament. In this concerted mechanism the Pi release is significantly accelerated compared to a spontaneous Pi release. We show how in the single-molecule experiment the force-dependent rate constants for the forward and reverse steps can be calculated without the use of adjustable parameters. The comparison of the predicted theoretical rate constants with experimental data from the single-molecule trajectories shows good agreement over a range of load forces from 0 to 6 pN. The strong analogy to the concerted binding-release mechanism for torque generation in F1-ATPase points to a shared mechanism for product release acceleration among motor enzymes. Our modeling approach complements recent computational work that considered the mechanochemical cycle of the myosin in its entirety.

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