Mining for proteins  pg. 3

Protein microarrays or “chips” provide another way to study interactions. The chips contain a variety of molecules that can bind specific proteins. Bound proteins, in turn, are detected through fluorescence labeling and other tagging techniques. This information is helping scientists understand how the cell operates at the molecular level, and how tiny changes in protein function can lead to disease.

Determining protein structure

A robotic machine punches protein-containing “gel plugs” out of a two-dimensional gel, based on coordinates determined by laser imaging. The gel plugs will be processed so that the proteins within them can be studied further. This and other technologies have greatly increased the speed and capabilities of proteomic research.
Photo by Anne Rayner
X-ray crystallography uses X-rays to determine the three-dimensional structure of the crystallized form of proteins and other important biological molecules. The technique has led to the development of drugs that specifically bind to and inhibit disease-related enzymes, including one essential for production of the human immunodeficiency virus, which causes AIDS.

It can take days, weeks or even years to crystallize proteins in order to study them. “But the payoff for all of this effort is well worth it,” says Walter Chazin, Ph.D., director of Vanderbilt’s Center for Structural Biology. “X-ray crystallography, as the core technique of structural biology and structural genomics, is providing a paradigm shift in the ability of scientists to understand, control and design new biomedical activities.”

Another way to determine protein structure is to analyze the way the nuclei of the atoms that make up the molecule “resonate” under the influence of radio waves in ultra-high magnetic fields, a technique called nuclear magnetic resonance spectroscopy.

In the 1980s, Wüthrich worked out a method for interpreting the NMR spectra of proteins in solution. Since then, he and his colleagues have determined the NMR structure of more than 50 nucleic acids and proteins, including prion proteins, which are thought to cause mad cow disease.

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