Did You Ever Wonder: Eva Nogales

Living cells have a cytoskeleton woven out of thousands of hollow fibers called microtubules, which give shape to cell walls and other structures, control the transportation of substances inside a cell, and play a vital role in cell division and proliferation. Microtubules themselves are made of a highly flexible protein called tubulin that is the key to the treatment of some types of cancer.

3-D atomic model of tubulin

This 3-D atomic model, nearly six years in the making, provided the first detailed look at tubulin, one of nature's most essential proteins and a key to many critical cell processes.

 

Because of tubulin's importance, scientists were keen to know its atomic structure. The search lasted more than 20 years and was successfully concluded in 1998 -- thanks in large part to the painstaking efforts of a then-32-year-old Spanish biophysicist who came to Berkeley as a postdoctoral fellow by way of England. Her name is Eva Nogales.

Born in Madrid, Nogales received her undergraduate degree in physics from the Universidad Autónoma de Madrid in 1989. Her Ph.D. in biophysics was earned from the University of Keele in England, with a thesis on how tubulin proteins are polymerized into long chains that form microtubules and other distorted polymers.

She joined Berkeley Lab in 1993 and began working with scientists Kenneth Downing and Sharon Wolf of the Life Sciences Division. They created the first 3-D atomic model of tubulin.

"If you know what a protein looks like at the atomic level, you can study and possibly learn to manipulate certain aspects of molecular behavior," says Nogales.

"An awful lot of people wanted to know the atomic structure of tubulin but were frustrated because it is so difficult to crystallize."

Nogales and her colleagues produced their model by polymerizing tubulin proteins under conditions similar to those in which microtubules are formed -- except for the additional presence of zinc. This forced the tubulin to form two-dimensional crystalline sheets, ideal for imaging by electron crystallography.

Over a five-year period the Berkeley Lab researchers recorded more than 4,000 images and electron diffraction patterns, from which Nogales carefully selected a data set for computerized reconstruction. Thirty plus years of scientific frustration ended with a phone message from Nogales to Downing announcing "Ken, it's done!"

The result was a 3-D model with a resolution of 3.7 angstroms that provided the first highly detailed look at tubulin, including the site where the protein interacts with the anti-cancer drug taxol.

Nogales is now a staff scientist with Berkeley Lab, an assistant professor with UC Berkeley, and an investigator for the Howard Hughes Medical Institute. She has a lab of her own, which has already made news by producing the first 3-D images of the protein complex that initiates DNA transcription.

Did You Ever Wonder Web Site
 
Ernest Orlando Lawrence Berkeley National Laboratory