BERKELEY, CA -- Microtubules are active protein polymers critical to the structure and function of cells and the process of cell division. In a living cell their growing ends constantly elongate and retreat in a thrashing frenzy of polymerization and depolymerization, like the writhing snakes of Medusa's hair. Known prosaically as "dynamic instability," this ongoing rapid growth and shrinkage is key to the diverse workings of microtubules in the cell.

For the first time, researchers have revealed at molecular level the forms taken by transitional structures of tubulin (the protein from which microtubules are formed) during the assembly and disassembly of microtubules. Details of these peculiar structures show how the binding to tubulin of the nucleotide guanosine triphosphate, GTP, controls activity at the growing end of the microtubule. Eva Nogales and Hong-Wei Wang of the Life Sciences Division of the Department of Energy's Lawrence Berkeley National Laboratory report their findings in the 16 June 2005, issue of the journal Nature.

"Tubulin is a major target for anticancer drugs, which can prevent the transition from growing to shrinking states or vice versa," says Nogales, who is also a member of Berkeley Lab's Physical Biosciences Division, an associate professor of biochemistry and molecular biology at the University of California at Berkeley, and a Howard Hughes Medical Institute Investigator. "We had previously produced high-resolution structures of stabilized tubulin structures, but nobody knew the structure of the transitional states. Our goal was to understand the process of microtubule assembly and disassembly."

"Our current work actually revealed the structures of different tubulin assemblies at the very ends of growing microtubules and depolymerizing microtubules," says Wang. "This allows a new understanding of the mechanism of microtubule dynamic instability, opening opportunities for new experiments testing the physiological
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Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
22-Jun-2005

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