Molecular helpers play key role in protein folding

by Daniel J. Fitzgibbons, Chronicle staff

Dan Hebert (left), assistant professor of Biochemistry and Molecular Biology, and Rob Daniels, Ph.D. student in Molecular and Cellular Biology, published their study of protein folding in the most recent issue of the journal Molecular Cell. (Stan Sherer photo)

t is a dance as old as life itself, the intricate folding of proteins into three-dimensional functional structures within cells. Now a new study led by assistant professor Dan Hebert of Biochemistry and Molecular Biology is shedding light on the role played by "molecular chaperones" in cellular maturation.

     In a study published Jan. 17 in the journal Molecular Cell, Hebert's team analyzes and documents the maturation of a cell taken from a flu virus. According to the team's findings, the position and location of the chaperones have evolved to optimize the folding process in the cell.

     Over the course of five years, Hebert's team painstakingly studied the maturation process - which actually takes about two minutes - to capture images of each stage that can be viewed as a movie.

     "The cell has figured out to do this in less than optimal conditions," he said. "This has important, fundamental implications for how chaperones operate."

     Hebert compares the process "as sort of an assembly line waiting to fold" as it is manufactured by the cellular machine known as the ribosome. The chaperones, he said, are strategically placed to guide the folding at key points in the process.

     That helper role is essential. "If you were placed in a room full of car parts, you probably wouldn't be able to build a car," he said. "But if I handed you each part as it was needed, you might be able to put it together."

     According to Hebert, deeper knowledge of the role of molecular chaperones could provide more understanding of protein folding and those diseases linked to misfolded proteins, such as albinism, emphysema, cirrhosis and Alzheimer's.

     Citing his team's work on the influenza virus, Hebert says, "If we learn to disrupt the folding, it could help to stop the flu."

     The study also lays the groundwork for further research on other types of cells, he said. "We should be able to predict how others behave," said Hebert, noting that some processes involves thousands of folds as the cells mature.

     Much of the experimentation was conducted by two graduate students, Brad Kurowksi, who is now attending medical school, and Rob Daniels, a doctoral student in Molecular and Cellular Biology. In fact, Daniels is listed as the lead author of the journal article - the role traditionally assigned to researcher who conducts the experiments. The other co-author is Arthur E. Johnson, a senior faculty member at Texas A&M University System Health Sciences Center, who provided some reagents to the researchers.

     The study was funded by the National Cancer Institute of the National Institutes of Health and the Edward Mallinckrodt Jr. Foundation.