The structure of a key part of the machinery that allows cells to divide has been identified by researchers at the University of California, Davis -- opening new possibilities for throwing a wrench in the machine and blocking runaway cell division in cancer.
"The structure of kinesin-5 is unexpected, and the implications are big -- it allows us to target it, for example in various forms of cancer," said Jawdat Al-Bassam, assistant professor of molecular and cellular biology at UC Davis, who led the project.
"This fills in a major missing piece, because for the first time we can understand how microtubule filaments can be linked together and slide past each other," he said.
The work will be published in the online journal eLife and is available at (elife website DOI)When a cell divides into two new cells, a structure called the mitotic spindle forms. Microtubules of protein fan out from each end of the cell, capture chromosomes and draw them apart into what will become the two new cells. Precise coordination of this process is crucial for cells to divide properly, and for avoiding birth and developmental defects.
Cancer cells divide continuously, so this process repeats itself much more often in cancer cells than in normal cells.
The kinesins are a large family of motor proteins that move items around inside cells, said Jonathan Scholey, professor of molecular and cellular biology at UC Davis and an author on the paper. Generally, they have two motor units at one end that can "walk" along a microtubule, dragging cargo attached to the other end of the protein.
Originally identified as a protein essential for mitosis in fungi, kinesin-5 was first purified about 20 years ago by Scholey's lab who found that it is unusual because it has motor units at both ends, allowing it to link two microtubules and walk them past each other.
"It's now understood to be absolutely essential for mitosis in
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University of California - Davis