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April 30, 2009

Researchers Find New Protein Function

Jon Kull (left) and Jared Cochran (photo courtesy of Joseph Mehling, Dartmouth)

A group of Dartmouth researchers has found a new function for one of the proteins involved with chromosome segregation during cell division. Their finding adds to the growing knowledge about the fundamental workings of cells, and contributes to understanding how cell function can go wrong, as it does with cancerous cells.

The researchers studied a protein called NOD, distantly related to the motor proteins that power diverse cellular activities, including intracellular transport, signaling, and cell division. They used x-ray crystallography at NSLS beamline X6A to determine its structure, and then they used enzyme kinetics to find out how it performed. While this protein is found in fruit flies, the results are helpful in determining how related proteins work in humans.

"This study on NOD provided evidence for a new way a kinesin motor could function," said Jared Cochran, a postdoctoral fellow at Dartmouth and the lead author on the study. "Rather than moving on its own, it hitches a ride on the ends of microtubules which results in a dynamic cross-linking between the arms of chromosomes and the cell’s growing spindle of microtubules. If NOD doesn’t function properly, then the two cells end up with either both or none of that particular chromosome, which is lethal [to the cell and the organism] in most cases."

With colleagues from Lawrence Berkeley National Laboratory, Stowers Institute for Medical Research in Kansas City, Missouri, and Kansas University Medical Center in Kansas City, Kansas, the Dartmouth group published their study in the Jan. 9, 2009, issue of the journal Cell.

"Before this study, it had been shown that kinesin motors either walked along their microtubule tracks or functioned to break microtubules apart," says Jon Kull, the senior author on the paper. "This work describes a novel mode for kinesin function, in which NOD does not walk, but rather alternates between grabbing on to and letting go of the end of the growing filament, thereby tracking the end as it grows. The diversity of function of these proteins is remarkable."

Protein NOD at the end of a microtubule

In addition to Cochran and Kull, authors on this study include Natasha Mulko from Dartmouth; Charles Sindelar from Lawrence Berkeley National Laboratory; and Kimberly Collins, Stephanie Kong, and R. Scott Hawley from Stowers Institute for Medical Research. Hawley is also affiliated with Kansas University Medical Center.