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Chemists show proteins behave differently inside cells than they do in water solutions

CHAPEL HILL -- In findings they believe are fundamentally important to both biology and medicine, chemists at the University of North Carolina at Chapel Hill have shown experimentally for the first time that proteins can behave differently inside cells than when taken out of those cells and studied in test tubes.

"For 40 years, we thought we could learn most everything about proteins by studying them in water, but this work shows we are missing important observations by looking at them just in water or other solutions," said Dr. Gary Pielak, professor of chemistry and lead author of the study. "Our work demonstrates that we need to study them under the conditions they are found in inside the cell."

The research is relevant to medicine because the protein is related to proteins associated with Parkinson's and Alzheimer's diseases and cancer, the scientists say.

"Proteins are the robots of the cell in that they perform countless functions including allowing cells to grow and reproduce," Pielak said. "Almost everything we know about them comes from research done in test tubes in water solutions. But inside cells, where proteins work, there are no dilute solutions because the interior is crowded with proteins, which take up about 40 percent of the volume."

Working under Pielak's supervision, Matthew Dedmon of Gastonia, N.C., used nuclear magnetic resonance (NMR) spectroscopy to examine what effects the crowded environment had on protein shape because the shape of a protein determines its function. The team found that a so-called "intrinsically unstructured" protein, which in water appears to have no fixed structure, shows a definite folded-up shape when inside cells.

Among other things, the experiments involved measuring the proteins with a nucleus of nitrogen known as N-15 and then recording and comparing their NMR spectrum both inside cells and outside cells under artificially crowded conditions.

A report on the findings was sc
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Contact: David Williamson
919-962-8596
University of North Carolina at Chapel Hill
13-Sep-2002


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