Mystery Of Vital Cell Protein Solved After 30 Years

BERKELEY, CA. -- A 30-year quest to solve the structure of one of the most important types of proteins in a living cell has been achieved. Scientists with the U.S. Department of Energy's Lawrence Berkeley National Laboratory have created the first 3-dimensional atomic model of tubulin, a protein that makes possible such vital life processes as cell division and the movement of materials within cells.

Eva Nogales, Sharon Wolf, and Kenneth Downing, biophysicists with Berkeley Lab's Life Sciences Division, announced the completion of their model in the January 8, 1998 issue of the scientific journal Nature. At a resolution of 3.7 angstroms, the model provides the first highly-detailed three-dimensional look at tubulin, including the site where the protein interacts with the promising anti-cancer drug taxol.

Tubulin is the protein that polymerizes into long chains or filaments that form microtubules, hollow fibers which serve as a skeletal system for living cells. Microtubules have the ability to shift through various formations which is what enables a cell to undergo mitosis or to regulate intracellular transport. The formation-shifting of microtubules is made possible by the flexibility of tubulin which is why scientists have sought to understand the protein's atomic structure since its discovery in the 1950s.

Interest in tubulin structure heated up intensely in recent years when taxol, a natural substance found in the bark of the Pacific yew tree (the name "taxol" has been trademarked by Bristol-Myers-Squibb), was shown in clinical tests to be an effective treatment for a number of cancers including ovarian, breast, and lung. Cancer occurs when cell division runs amok.

By binding to tubulin and causing the protein to lose its flexibility, taxol prevents a cell from dividing. With better knowledge of tubulin structure and its interaction with taxol, scientists believe that an even more effective anti-cancer drug, one

Contact: Lynn Yarris
DOE/Lawrence Berkeley National Laboratory

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