Structural transitions in kinesin minus-end directed microtubule motility

Area of Science:

• Molecular Biology
• Biophysics
• Cell Biology

Background:

• Kinesin motor proteins are essential for cellular functions like spindle assembly and vesicle transport.
• The precise structural transitions enabling kinesin force generation remain incompletely understood.

Purpose of the Study:

• To elucidate the structural dynamics of kinesin during its mechanochemical cycle.
• To identify the key structural elements responsible for force production in kinesin.

Main Methods:

• High-resolution structural analysis of kinesin motor proteins.
• Characterization of intermediate states within the kinesin mechanochemical cycle.

Main Results:

• New high-resolution structures reveal transitions in the kinesin mechanochemical cycle.
• Identified a post-hydrolysis state with bound ADP and free phosphate.
• Demonstrated that microtubule binding triggers ADP release and central β-sheet twisting, initiating the power stroke upon ATP binding.
• Observed β-strand-to-loop transitions upon microtubule release, leading to Pi release and the recovery stroke.

Conclusions:

• The kinesin β-sheet acts as the motor spring, undergoing conformational changes to generate force.
• Structural transitions, including β-sheet twisting and strand-to-loop rearrangements, are critical for kinesin's motor function.