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Life's smallest motor, cargo carrier of the cells, moves like a seesaw
Date:2/18/2010

kinesin motors have enabled researchers to piece together the protein's three-dimensional structure. But these images don't reveal how it works.

"The problem is that it is not until the protein motor binds to a microtubule that structural rearrangements occur that enable ATP hydrolysis, the process that transfers energy from ATP to kinesin," says Downing.

To image kinesin at this critical stage, Downing and Sindelar turned to cryoelectron microscopy, which is a type of electron microscopy in which the sample is studied at extremely low temperatures. The technology is used by structural biologists to image proteins and other molecules as they appear in real-world conditions, in this case a kinesin protein attached to a microtubule.

The technique yielded 8 to 9 angstrom-resolution snapshots of the kinesin motor at four stages of the motor's cycle as it moves along a microtubule. One angstrom is one-ten billionth of a meter. Using these images as a guide, the researchers then "dropped in" even higher resolution crystallographic images of kinesin's components. This step enabled them to derive atomic-level structural models of kinesin in action.

"Collectively, this work provides a detailed molecular explanation for kinesin's microtubule-attached power stroke," says Downing. "In other words, we can see it how it works in real life. We looked at kinesin in different phases, and learned what causes it to move from one conformation to another, which is how it pulls cargo along the microtubule."

In addition to further elucidating a key biological process, Downing and Sindelar's research may inform the development of disease-fighting drugs. One of kinesin's main jobs is moving chromosomes apart during cell division. Anything that blocks this process will lead to cell death, which is the basis of several cancer therapies such as taxol.

"New insights into how kinesin works could allow scientists to develop drugs that target a
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Contact: Dan Krotz
dakrotz@lbl.gov
510-486-4019
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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