Single amino acid mutation dramatically alters direction of a molecular 'motor'

DURHAM, N.C. -- Researchers from Duke University Medical Center and Tohoku University, Japan, report finding two single amino acid mutations that disrupt the sense of direction in a molecular "motor," and creating one for the first time that is equally likely to travel either up or down its track.

Molecular motors are proteins made up of amino acids like any other protein in a cell. They move along tiny filaments, called microtubules, as they transport vesicles around the cell or herd chromosomes during cell division. Most motors move toward the fast-growing end of these microtubules, but some move toward the opposite, more stable end of the microtubules. Until now, it was thought that these motors could only do one or the other.

Scientists believe that malfunctioning molecular motors might be responsible for some diseases caused by incorrect distribution of chromosomes during cell division, such as Down syndrome. By understanding how motors work, how they organize chromosomes and how they lead the cell through the division process, researchers hope to be able to understand what causes these diseases and how to prevent them.

Changing a certain amino acid in a molecular motor called Ncd, which was discovered at Duke, caused an "astonishing" result in the motor's behavior, said Sharyn Endow, lead author of the research report, which appears in the Aug. 24 issue of the journal Nature.

"We were able to create the very first bi-directional molecular motor by changing only a single amino acid," said Endow, professor of microbiology at Duke. "We didn't even know it could be done, and it's very surprising that a single mutation can do it. This solves the question of the mechanism of directionality for Ncd and probably applies to other motor proteins as well."

From the time Endow discovered Ncd in fruit flies about 10 years ago, the little motor has been an enigma. At the time, it was the first molecular motor of its kind that moved toward the

Contact: Joanna Downer
Duke University Medical Center

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