A raison d'etre for heat-shock proteins.

A raison d'etre for heat-shock proteins

Cells of all organisms respond to heat or other stresses by making complex molecules called heat-shock proteins. Ohter heat-shock proteins exist in unstressed cells and seem to play a role in normal cell maintenance. Such a ubiquitous group of proteins, conserved through billions of years of evolution, must be important -- yet no one has been able to say for sure just what purpose they serve.

Now, two separate groups of scientists have provided a partial answer. They report that one family of heat-shock proteins helps move other critical proteins across membranes inside the cell.

Proteins are essential to cell reproduction and functioning. But where these proteins are produced may not be where they are needed. Inside cells with nuclei are specialized structures called organelles that are separated from the rest of the cell by a membrane. For example, an organelle called the mitochondria requires protein and oxygen to produce the high-energy molecule ATP, one of the cell's basic fuels. Cellular protein, however, is created outside the organelles in the general area called the cytoplasm, and must cross a membrane to get into the organelle that needs it.

Just as it is difficult to thread a needle with tightly bunched-up string, it is difficult for globular proteins to pass through membranes. Sometimes, important proteins use heat-shock proteins to help get across the membrane and into the targeted organelle, report scientists from the University of California at Berkeley, the University of Wisconsin in Madison and Rockefeller University in New York City, in two papers in the April 25 NATURE. The scientists speculate heat-shock proteins assist other proteins through membranes by grabbing them and unfolding them, thus presenting the organelle with a less globular, straightened protein.

Both groups of scientists looked at the same kind of heat-shock proteins, but one group studied those proteins in yeast cells while the other looked at an in vitro simulated cell system. Both found that without heat-shock proteins, other important proteins built up outside the organelles, unable to enter.

One of the proteins unable to cross membranes on its own is critical for making ATP in the mitochondria; without ATP a cell would die, and yeast cells unable to make heat-shock proteins don't last long, says Berkeley researcher Raymond Deshaies. His group looked at the buildup of only two proteins in yeast cells lacking heat-shock proteins, but he says many other proteins probably depend on heat-shock proteins to assist their movement across membranes, and heat-shock proteins probably perform many other functions as well.

Heat-shock proteins might also readjust incorrectly folded proteins by grabbing them, unfolding them and letting them fold back together in the correct way, says molecular biologist Hugh Pelham of Cambridge University, in an article accompanying the papers. Such proteins, he suggests, might be a boon to genetic engineers and othes who are trying to pull individual protein molecules from the insoluble globs of protein often produced by engineered cells.