Public Release: 

New Kind of Chaperone Discovered: AIDS Hormone Detection

Northwestern University

EVANSTON, Ill. --- Heat shock proteins, or "chaperones," are known to protect the body from stress. They help refold proteins that have become damaged due to intense heat, exposure to toxins or metals or lack of oxygen.

But researchers at Northwestern University and the Mayo Clinic have discovered a new kind of chaperone --- one that holds proteins in hormone receptors in an intermediate stage so that they will be more sensitive to the presence of hormones.

"It produces a hair-trigger response to the hormone," said Richard Morimoto, John Evans Professor in Molecular Biology and chair of the department of biochemistry, molecular biology and cell biology at Northwestern University.

Once contact is made with the hormone, the receptor binds to the hormone and becomes folded and active, inducing gene expression, the researchers report in the Dec. 6 issue of the journal Science. "This finding formally expands our understanding of what molecular chaperones are," Morimoto said.

"This is another kind of molecular chaperone," said David O. Toft, professor of biochemistry and molecular biology at the Mayo Clinic in Rochester, Minn., and co-author of the report. "This opens up the possibility that there may be a variety of chaperones performing different kinds of functions within the body."

Another report in Science by a team of researchers headed by Johannes Bucher at the University of Regensberg, Germany, agrees with the Morimoto group's findings.

A third report, by a team headed by Richard F. Gaber at Northwestern and Susan Lindquist at the University of Chicago, describes experiments that indicate that another protein, known as Cpr-7, binds to the heat shock protein Hsp90, and is essential for normal cell growth.

The paper by Morimoto, Toft, and graduate student Brian Freeman identifies two new proteins, called Cyp-40 and p23, as molecular chaperones. They act in a manner very similar to the heat shock protein hsp90, folding proteins into an intermediate, half-way state. These proteins are part of the steroid receptor complex, the paper reports.

The collaborative research was an outgrowth of a study Toft was conducting of the large, multi-protein complexes that surround the steroid receptors. He found that two of the proteins in the complex were heat shock proteins, hsp70 and hsp90, and theorized that the remaining four proteins in the complex might have similar or related functions.

Morimoto, having developed a new way to study the function of chaperones, contacted Toft to determine if these proteins acted as molecular chaperones. Two of the four proteins proved to act like chaperones.

Proteins are made up of long strings of amino acids that must be folded in precisely the right way to perform their tasks within the cell. When they become damaged, due to environmental and physiological stresses including intense heat, exposure to toxins or metals, or because of lack of oxygen, they become unfolded. Previous research has determined that the chaperone protein hsp 70 interacts with a second, called hdj-1, to refold the proteins.

In research published last June in the EMBO Journal (the journal of the European Biology Organization), Morimoto and Freeman reported that a third chaperone, called hsp90, converted the proteins into an intermediate state that could then be acted on by the other two.

In connection with the current article, Toft said, the newly discovered chaperones not only make the receptors more sensitive to hormones, but probably have a more general impact on the cell, helping to fortify the cells' defense against heat and other stresses.



Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.