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Mystery Of Vital Cell Protein Solved After 30 Years

that interacts only with the tubulin of cancerous cells, could be synthesized.

"An awful lot of people have wanted to know what tubulin looks like at the atomic level," says Nogales. "The knowledge gained from this model should be of invaluable help in understanding the microtubule system in the cell."

Tubulin is a "heterodimer" protein, meaning it is comprised of a pair of polypeptide chains -- called monomers -- that differ in the sequence of their amino acids. The model presented by Nogales, Wolf, and Downing, shows that each tubulin monomer -- the alpha and the beta -- is a compact molecular structure with three functional components or domains, one that binds to nucleotides, one that binds to drugs like taxol, and one that looks to be a binding site for other proteins.

"The interaction between domains is very tight so that the effects that nucleotides, drugs, and other proteins have on tubulin are firmly linked," says Nogales. "The assembly of tubulin and its regulation through dynamic instability results from the fine tuning of the three components."

To produce their model, the Berkeley Lab researchers first polymerized tubulin proteins under the same conditions in which microtubules are formed except for the additional presence of zinc. The zinc prevents tubulin chains from curling around into hollow fibers. Instead, the polymerized tubulin forms two-dimensional crystalline sheets that are ideal for imaging by electron crystallography. The use of electron-based rather than the x-ray-based crystallography techniques customarily employed in protein studies was crucial to the model's 3.7 angstrom resolution.

"Working with x-ray crystallography requires much more protein than electron crystallography," says Downing. "Obtaining diffraction patterns with an electron beam enables us to work with crystals only one molecule in thickness, giving us our high resolution."

The final 3-D model is
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
8-Jan-1998


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