Tension-induced suppression of allosteric conformational changes coordinates kinesin-1 stepping

Area of Science:

• Molecular motor function
• Cellular mechanics
• Biophysics

Background:

• Kinesin-1 uses two motor domains (heads) to walk along microtubules via ATP hydrolysis.
• The mechanism preventing premature binding of a detached head to microtubules remains unclear.
• The neck linker's role in coordinating head movement is not fully understood.

Purpose of the Study:

• To investigate the role of the neck linker in Kinesin-1's coordinated head movement.
• To elucidate the mechanism preventing premature microtubule binding of a detached head.

Main Methods:

• Structural analysis of nucleotide-free Kinesin-1 heads.
• Molecular dynamics simulations.
• Single-molecule fluorescence assays.

Main Results:

• A bulge near the neck linker's base creates asymmetric mobility constraints.
• Neck linker tension, influenced by this bulge, suppresses premature head binding.
• Simulations and assays confirmed the hypothesis of tension-dependent regulation.

Conclusions:

• Neck linker tension is a key factor in Kinesin-1's processive movement.
• A tension-dependent allosteric mechanism coordinates the two motor heads.
• Neck linker tension modulates conformational changes, not directly the nucleotide state.