Positional Isomers of a Non-Nucleoside Substrate Differentially Affect Myosin Function.

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• Molecular motors, like myosin, convert chemical energy into mechanical work for cellular functions.
• Myosin dysfunction is linked to various diseases, highlighting the need for motor control.
• Current methods for controlling molecular motors are limited.

Purpose of the Study:

• To investigate positional isomerism as a method for controlling myosin motor function.
• To demonstrate that structural variations in energy sources can modulate myosin's mechanical output.
• To understand how different isomers affect myosin's mechanochemical cycle.

Main Methods:

• Utilized three positional isomers of a synthetic non-nucleoside triphosphate as energy sources for myosin.
• Performed ensemble and single-molecule experiments to measure myosin's force and motion.
• Employed computational analysis to correlate experimental findings with myosin's mechanochemical cycle steps.

Main Results:

• Demonstrated significant alterations in myosin's force and motion generation using different isomers.
• Showed that positional isomerism provides intrinsic control over myosin's mechanical activity.
• Identified distinct effects of each isomer on specific steps within myosin's ATP hydrolysis cycle.

Conclusions:

• Positional isomerism is a viable strategy for precisely controlling myosin motor function.
• Subtle changes in abiotic energy source structure can tune myosin's force and motility without altering the motor protein itself.
• This approach offers potential for therapeutic interventions targeting myosin-related pathologies.