Monday, June 15, 2009

Proteins Promising for Drug Development

Some intracellular engines are more efficient than others

A kinesin motor carrying a cargo along a microtubule.

Insights into motor proteins called kinesins may fuel drug development because of their importance to cellular function, researchers report. The group is attempting to understand how kinesins transport cargos within cells in order to identify future therapeutic targets.

"We are trying to further understand the coordination between the two motor domains in kinesins," said William O. Hancock, PhD, an associate professor of bioengineering at Pennsylvania State University in University Park, Pa. Kinesins are two-headed nanomachines that move cargo along microtubules within cells. Dr. Hancock’s team has shown that kinesins with longer linkages between their two heads are less efficient than those with shorter linkages. (Muthukrishnan G, Zhang Y, Shastry S, et al. The processivity of kinesin-2 motors suggests diminished front-head gating. Curr Biol. 2009;19(5):442-447.)

"This is important for long distance transport in cells," Dr. Hancock said in an e-mail to PFQ. "The mechanochemical coordination between the two heads is fundamental to their mechanism, but it is difficult to unravel because of the interdependence of the activities of the two heads."

Dr. Hancock said his group has found that motors with extended neck linkers show less coordination between the two motor domains.

Another focus of his lab’s work is use of kinesin motors in lab-on-a-chip technologies. "These nanomotors have been integrated with microfluidic channels as a potential direction toward hybrid lab-on-a-chip devices where molecules are transported by kinesins and microtubules instead of fluid pumping,

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