Kinesin, 30 years later: Recent insights from structural studies.

Area of Science:

• Cellular Biology
• Biochemistry
• Structural Biology

Background:

• Motile kinesins are ATP-hydrolyzing motor proteins that generate force and movement along microtubules.
• Kinesin motor domains bind both ATP and microtubules, facilitating their function.
• The most studied kinesin moves towards the microtubule plus-end via a two-head mechanism.

Purpose of the Study:

• To review the structural mechanism of kinesin motor protein movement.
• To elucidate the role of neck linker conformations in kinesin's unidirectional motion.
• To understand the structural basis of kinesin's processivity.

Main Methods:

• High-resolution studies utilizing cryo-electron microscopy and X-ray crystallography.
• Analysis of complexes between the kinesin motor domain and tubulin.
• Investigating structural changes upon ATP binding to microtubule-bound kinesin.

Main Results:

• ATP binding to a kinesin head induces conformational changes in motor subdomains.
• Neck linker docking onto the motor core is crucial for directing the other head towards the microtubule plus-end.
• The interplay between neck linker docking and subdomain orientation explains kinesin's processivity.

Conclusions:

• High-resolution structural data clarifies the mechanical steps of kinesin-microtubule interaction.
• The neck linker's conformational changes are central to kinesin's directional movement and processivity.
• Future studies can extend these insights to other kinesins, linking sequence to diverse functions.