Nobelist Dr. Johann Deisenhofer, professor of biochemistry and senior author of the study, and Dr. Gabrielle Rudenko, assistant instructor of biochemistry and lead author of the study, solved the three-dimensional structure of a low-density lipoprotein (LDL) receptor's extracellular domain. LDL is known as the "bad" cholesterol because it deposits fat-like substances that clog arteries.

The LDL receptor binds LDL in the liver and clears it from the blood by pulling cholesterol inside the cells, where it is metabolized to replenish hormones, the cell membrane, vitamin D and other products.

"This research will help scientists understand the mechanics of how our bodies absorb cholesterol from the blood," Deisenhofer said. "Hopefully, we can use the information to develop treatments for people with mutations that diminish the functions of their LDL receptors."

UT Southwestern Nobel laureates Dr. Michael Brown and Dr. Joseph L. Goldstein also assisted in the study, which will be published in the Dec. 20 issue of Science. An early version is listed online at Science Express.

There are about 1,000 LDL receptor mutations that have been found in people with familial hypercholesterolemia (FH). FH is one of the most common "single-gene" inherited diseases and affects about one in every 500 people, Rudenko said. By revealing the structure of the receptor, scientists now can begin to understand why these different mutations cause FH, a disorder that results in very high cholesterol levels, atherosclerosis and increased risk of having a heart attack early in life.

"If you understand the basic biological mechanisms underlying a disease, you can hope to come up with strategies to battle that disease," Rudenko said. "Solving
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Contact: Scott Maier
Scott.Maier@UTSouthwestern.edu
214-648-3404
UT Southwestern Medical Center
6-Dec-2002