Robust processivity of myosin V under off-axis loads.

Area of Science:

• Cellular Biology
• Molecular Motors
• Biophysics

Background:

• Myosin V is a dimeric motor protein essential for intracellular organelle transport along actin filaments.
• Processive movement of myosin V is crucial for efficient cargo delivery but can be hindered by variable cellular conditions and off-axis loads.
• The regulation of myosin V's stepping mechanism under load, particularly in vivo, remains poorly understood.

Purpose of the Study:

• To investigate how myosin V maintains processive stepping under various off-axis loads encountered in cellular environments.
• To elucidate the role of inter-head coordination and biochemical kinetics in load adaptation.
• To understand the structural contributions, such as the 6IQ lever, to myosin V's in vivo functionality.

Main Methods:

• Experimental measurement of off-axis load effects on individual actomyosin V bonds at varying angles.
• Analysis of coordination between myosin V's two heads under applied loads.
• Assessment of myosin V's processive stepping behavior in response to diverse load conditions.

Main Results:

• Myosin V demonstrates high processivity even under diagonal loads, attributed to asymmetrical ADP affinities between its heads.
• The native 6IQ lever element plays a significant role in optimizing the coordination between myosin V's subunits.
• These findings reveal a sophisticated load-adaptation mechanism inherent to myosin V's structure and kinetics.

Conclusions:

• Myosin V is intrinsically designed for robust intracellular transport, capable of navigating complex cellular environments and loads.
• Asymmetrical ADP affinities and optimized subunit coordination are key to myosin V's resilience and processivity under load.
• The study underscores myosin V's specialized role as an efficient intracellular transporter.