A force-dependent state controls the coordination of processive myosin V

Area of Science:

• Molecular Biology
• Biophysics
• Cellular Motor Proteins

Background:

• Myosin V is a highly processive molecular motor crucial for intracellular transport.
• Its structure and kinetics are adapted for efficient, multi-step movements along actin filaments.
• Understanding the coordination between its two heads is key to elucidating its function.

Purpose of the Study:

• To investigate the coordination mechanism between the two heads of myosin V during hand-over-hand stepping.
• To determine how external forces affect the kinetics and cycling of individual myosin V heads.

Main Methods:

• Utilized a modified laser-trap microscope to apply controlled forces (approx. 2 pN) to single-headed myosin V molecules.
• Simulated forces experienced by the rear and lead heads during processive stepping.

Main Results:

• Applying forward force caused minimal changes in myosin V kinetics.
• Applying backward force significantly reduced the cycling rate of the myosin V head.
• These findings suggest a coordination mechanism involving force-dependent regulation.

Conclusions:

• The coordination of myosin V stepping is likely mediated by strain-generated inhibition of the lead head.
• This mechanism ensures efficient and directed movement along actin tracks.
• The study provides insights into the molecular basis of processive motor function.