( e computational analysis and analyzed t...)Researchers image molecular motor structural changes

The researchers then took those high-resolution models and combined them with models of kinesin and microtubule structures rendered using another technology, x-ray crystallography. In this approach, scientists send an x-ray beam through a crystallized protein target, in this case, the motor molecules or microtubules, separately. Detectors capture the signal as it exits the target and computers re-create a three-dimensional model. Researchers have not yet been able to image motors bound to micotubules using x-ray methods due to technical challenges, they said.

According to the researchers, the new motor-microtubule models provided structural details of the motor-microtubule interactions that had not been observed previously.

The researchers believe their findings may lead to new insights into a number of diseases, including some neuromuscular conditions, such as Charcot-Marie-Tooth disease. These disorders are thought to be linked to deficiencies in transport by the molecular motors of chemical neurotransmitters that carry messages between nerve cells. Down syndrome, in which chromosomes do not divide properly in egg cells, also is thought to be caused by defects in kinesins. Finding methods to stimulate kinesin activity might help in the treatment of these human diseases, the researchers said.

Conversely, drugs that inhibit kinesin activity might be a potential approach to slowing the uncontrolled cell division of cancer. For example, the drug Taxol, which is used to treat breast and ovarian cancers, works by stabilizing microtubules. But the problem with using Taxol as a general inhibitor of cell division is that it works on all dividing cells, not just those involved in tumors or cancers, and so causes unwanted side effects, such as hair loss.

"With this new information about kinesins and how they interact with microtubules, the hope is that we will
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Source:Duke University Medical Center