Fall 2007

Know How

Proteins are the workhorses inside every cell—yours, mine, a flower’s, all living beings—that perform the duties that keep our cells functioning properly. But proteins are too small to see, even with the most powerful microscopes. Instead, scientists jump through various hoops to figure out their structures. Here’s one method they commonly use:

Illustrations by H. Adam Steinberg

Choose an important protein. Because coming up with a 3-D image of a protein’s structure is costly and labor-intensive, it is important to choose your protein wisely. Often, scientists want to know the shape of proteins associated with particular diseases so that they might develop new treatments or pharmaceutical agents to target the cause of the disease.

Generate a whole bunch of molecules of that protein. Scientists can trick bacterial cells to produce a particular protein by inserting DNA that instructs the cell to crank out copies of the desired protein. Another method uses cellular machines to make proteins in a test tube.

Coax those proteins to form crystals. Working with a solution full of protein, scientists adjust temperature, pH, salts and other components in a painstaking process to encourage crystals to form and grow. As proteins crystallize, their molecules line up in an ordered way, like individual chairs that stack together to make a tower.

Blast one of the best crystals with X-rays. When a narrow beam of X-rays penetrates the ordered protein molecules in a crystal, the rays bend as they pass by atoms in protein molecules. Software programs then read the pattern created by the X-rays and deduce a 3-D model of the protein molecule.

Refine the protein’s 3-D structure. A human hand is always needed to fine-tune the protein’s shape. Because this whole process is so complicated, less than 3 percent of attempts result in successful 3-D structures. At this point, each of these models costs around $80,000 to create. Work at the UW–Madison’s Center for Eukaryotic Structural Genomics, part of the biochemistry department, is aiming to improve that success rate and lower the price of the process.

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