- Open Access
Kinesin-14: the roots of reversal
© Cross; licensee BioMed Central Ltd. 2010
- Received: 14 July 2010
- Accepted: 4 August 2010
- Published: 16 August 2010
Kinesin-14 motor proteins step towards microtubule minus ends, in the opposite direction to other kinesins. Work on the still-enigmatic kinesin-14 mechanism published in BMC Structural Biology shows that the carboxyl terminus of the motor head undergoes a dock-undock cycle, like that of plus-end-directed kinesins.
See research article: http://www.biomedcentral.com/1472-6807/10/19
- Carboxyl Terminus
- Cryoelectron Microscopy
- Motor Head
- Published Crystal Structure
- Lever Position
For the plus-end-directed kinesin-1, kinesin-3 and kinesin-5, crystallography has revealed that the flexible carboxyl terminus of the head (called the 'neck-linker') can dock into a slot on the main part of the head, with the amino terminus lying alongside or wrapping over it. Recent simulations suggest that in kinesin-1, this interaction between the amino and carboxyl termini contributes substantially to the free energy of neck-linker docking , lending new life to the proposal, originally made a decade ago , that neck-linker docking is itself the force-generating event for kinesin-1, equivalent to the lever arm action proposed for myosins. The carboxyl terminus of kinesin-14 is not seen in existing crystal structures. But in the new kinesin-14 crystal structure of Heuston et al. , the carboxyl terminus of one of the two heads is seen to anneal into a site on the main part of the head in much the same way as the carboxy-terminal neck-linker of plus-end-directed kinesins. The docking occurs in the head with the 'post-stroke' lever position, suggesting that lever motion and docking are coupled. Both heads in the new structure contain ADP, but the occupancy is reduced in the head with the docked carboxyl terminus and post-stroke lever position. Heuston et al. speculate that their post-stroke structure may correspond to a no-nucleotide microtubule-bound state of the motor, so that force generation is coupled to ADP release.
Here again, high-resolution cryoelectron microscopy can help. Hirose and colleagues  examined Kar3, a minus-end-directed kinesin-14, and found large-scale melting of the alpha4 relay helix on going from the state with bound ATP analog AMPPNP to the empty state, but any effects on the carboxyl terminus or coiled-coil tail are unknown as they were not included in the motor construct used. Movement of the alpha4 helix and docking of the neck-linker has been confirmed in several plus-end-directed kinesins in complex with microtubules .
The new work of Heuston and colleagues  shows that in kinesin-14, as in other members of its extended family, docking and undocking of the carboxy-terminal residues of the head can occur during ATP turnover. The outstanding problem now is to work out the molecular mechanism by which the coiled-coil lever of kinesin-14 is driven from pre-stroke to post-stroke positions and back again. One possibility is that residues on the microtubule contribute. Whatever the answer may be, it is a safe bet that the kinesin-14 mechanism holds yet more surprises in store.
I thank Linda Amos, Andrew McAinsh and Anne Straube for helpful comments and Marie Curie Cancer Care for program support.
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