New cancer therapies: solving the protein motor puzzle

A research team at Oregon State University has recently published findings that solve a longstanding puzzle regarding the design of protein motors, with implications in cancer therapy.

Jul 16, 2018

Scientists from Oregon State University College of Science (OR, USA) have uncovered the structural characteristics of kinesin-14 that give way to its preference of a two-microtubule track. The findings, published in Current Biology, have implications in the design of new cancer therapies as some cancer cells depend on kinesin-14 to proliferate.

Kinesins are protein-based motors that convert chemical energy into mechanical energy, generating directional movements necessary in cells. Microtubules are tubular structures utilized by kinesins to carry cargo, such as organelles and vesicles, from the center to the periphery of a cell. They are made up of two distinct ends, termed the plus and minus ends.

"Kinesin-14s contribute to the assembly of an oval-shaped superstructure called the spindle," commented corresponding author Weihong Qiu, assistant professor of physics. "The spindle functions to ensure chromosomes are accurately separated between daughter cells during cell division."

It is known that most kinesins only interact with one microtubule at a time; however, kinesin-14 preferentially binds to two different microtubules – one with its feet and one with its tail.

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The researchers studied kinesin-14 from fungus and fruit flies with the aim of identifying why kinesin-14 binds to two microtubules at a time. The results reveal kinesin-14 to have a stiff waist, rather than a flexible one, which separates the kinesin feet from the tail and appears to be the reason for the preference shown by the protein motor.

"Nature through evolution came up with a remarkable plan in terms of the design of the motor protein," Qiu remarked. "Most kinesin-14 motors function inside the spindle and need to interact with two different microtubules rather than one. Our research reveals that to accommodate that functional need, these kinesin-14s have evolved to have a rigid middle piece."

When the stiff waist was replaced by a flexible polypeptide linker, the ability of the kinesin to function normally was severely compromised. The fungal kinesin-14 was shown to change direction, moving now to the minus end of microtubules, while the fly kinesin-14 shifted from being non-processive to a processive, minus-end directed motor.

The fly kinesin-14 was also shown to no longer be able to bind two microtubules at once. Qui concluded, “Our results imply a novel therapeutic approach, which is to target the waist region of the motor protein."

"If the kinesin-14 motor can bend at the waist like a gymnast, then its ability to interact with two microtubules is lost, and so is its function. Now drugs can be identified that modify the rigidity of the waist region."


Wang P, Tseng KF, Gao Y, Cianfrocco M, Guo L and Qiu W. The central stalk determines the motility of mitotic kinesin-14 homodimers. Curr. Biol. (Epub ahead of print) doi:10.1016/j.cub.2018.05.026 (2018);

Jasmine Harris

Digital Editor, Future Science Group

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