April 25, 2008

Discovery Lecturer offers new view of proteins

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Zhaohua Ding, Ph.D., left, snaps a photo of his son, Michael, with Kurt Wüthrich, Ph.D., following last week’s Discovery Lecture. (photo by Mary Donaldson)

Discovery Lecturer offers new view of proteins

We may think of proteins as invisible nutrients in our diet, but these minuscule molecules have shape and structure that determines their function in our bodies.

In 2002, Kurt Wüthrich, Ph.D., was awarded the Nobel Prize in Chemistry for his instrumental role in developing a new way of determining the three-dimensional structure of proteins, called nuclear magnetic resonance (NMR) spectroscopy.

At last week's Discovery Lecture, Wüthrich gave a brief history of the evolution of this technique and the various ways he and colleagues have used it to construct detailed three-dimensional images of important biomolecules — from the hemoglobin molecule that transports oxygen through our bodies, to the poorly-understood prion proteins thought to cause deadly brain disorders like “mad cow” disease and Creutzfeldt-Jakob disease.

Wüthrich entered the field of structural biology in 1968 by studying hemoglobin. An athlete living at a high elevation in Switzerland, Wüthrich noted that hemoglobin was the reason “I was always running out of breath during physical exercise.”

In one early study, Wüthrich used NMR to determine the structure of hemoglobin from his own blood.

But, he notes, that without the earlier “scaffold” obtained with the traditional technique of X-ray crystallography, “NMR alone could not have determined the structure from scratch.”

More recently, Wüthrich's group has used NMR to define some structural and dynamic aspects of prions that might account for their inefficient transmission between species.

Unlike the early days of NMR, researchers can now determine de novo structure using the technique, without needing an X-ray crystal structure as a template.

NMR has contributed about 10,000 of the 50,000 known protein crystal structures — including, he noted as he showed his final slide — a protein eerily shaped like his home country of Switzerland.

Wüthrich is professor of Structural Biology at The Scripps Research Institute in La Jolla, Calif., and a professor of Biophysics at ETH Zürich in Switzerland.

For a complete schedule of the Discovery Lecture Series and archived video of previous lectures, go to www.mc.vanderbilt.edu/discoveryseries.