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Denatured Proteins Rescued By Trio Of Chaperones

Date:
July 15, 1998
Source:
University Of Chicago Medical Center
Summary:
You can't unfry an egg--or maybe you can. Researchers from the Howard Hughes Medical Institute at the University of Chicago report in the July 10 issue of Cell that a powerful combination of heat shock proteins (Hsps) can return aggregated proteins, until now thought to be permanently entangled, to their functional, native states.

You can't unfry an egg--or maybe you can. Researchers from the Howard Hughes Medical Institute at the University of Chicago report in the July 10 issue of Cell that a powerful combination of heat shock proteins (Hsps) can return aggregated proteins, until now thought to be permanently entangled, to their functional, native states.

Previously, scientists thought that Hsps could only prevent proteins from aggregating as temperatures rise. But now, Susan Lindquist, Ph.D., and colleague John Glover, Ph.D., have shown that protein snarls can actually be rescued by Hsp104 with the assistance of two other heat shock proteins.

Heat is a protein's enemy. As an egg fries, its proteins, which are made of chains of molecules called amino acids precisely folded into spirals, loops and sheets, begin to loose their shape. Sticky bits from the interior of the protein get exposed, and adhere to each other, forming disordered globs, or aggregates (this is why egg whites change from a clear liquid-like state to a white solid). In the body, heat stress can do the same thing to proteins, making them dysfunctional.

When exposed to sudden shifts in temperature, all organisms make heat shock proteins, otherwise known as chaperones, which protect (to some extent) against denaturation. The chaperone's job is to protect unfolded proteins from getting into more trouble (aggregating) until they have had a chance to refold to their normal, functional form.

"The general strategy for cells is to prevent aggregation from happening in the first place," says Lindquist, Howard Hughes Investigator and professor in the Department of Molcular Genetics and Cell Biology. "We thought that Hsps bind to sticky surfaces presented by denatured proteins to prevent them from interacting and forming a blob, and they do. But now we have shown that at least one heat shock protein, namely Hsp104, has the ability to rescue proteins that have already aggregated. This ability is essential to the survival of cells facing extreme heat."

To find out where and how Hsp104 works, the researchers tested its ability to prevent aggregation and promote refolding of heat denatured firefly luciferase. They found that Hsp104 alone could not untangle the clusters. However, when other heat shock proteins from yeast were added, reactivation of luciferase was observed.

Lindquist and Glover pinpointed two heat shock proteins that were observed to interact with Hsp104-Hsp40 and Hsp70. When these chaperones were added to the aggregated luciferase together with Hsp104, there was a profound increase in the amount of recovered functional protein.

"When we put the two elements together, the Hsp40 and 70 plus Hsp104, there was a synergistic effect and we saw incredible amounts of refolding," says Glover.

Lindquist and Glover think that Hsp40 and Hsp70 help to partially stabilize proteins as they begin to aggregate. Then, Hsp104 helps the glob come apart so that Hsp40 and Hsp70 can refold individual proteins to their native states.

"Understanding how Hsp104 works could help us to better understand protein folding disorders, such as Alzheimer's and mad cow disease," says Lindquist. "It could also shed light on how disease organisms that are carried by cold blooded insects survive the sudden temperature transition as they are injected into their warm-blooded hosts," says Glover.

Chaperones from bacteria, plants, lower animals and humans are virtually identical. This means that they probably evolved to protect the very earliest organisms to inhabit our planet and have remained essentially unchanged through billions of years.


Story Source:

The above story is based on materials provided by University Of Chicago Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Chicago Medical Center. "Denatured Proteins Rescued By Trio Of Chaperones." ScienceDaily. ScienceDaily, 15 July 1998. <www.sciencedaily.com/releases/1998/07/980715083913.htm>.
University Of Chicago Medical Center. (1998, July 15). Denatured Proteins Rescued By Trio Of Chaperones. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/1998/07/980715083913.htm
University Of Chicago Medical Center. "Denatured Proteins Rescued By Trio Of Chaperones." ScienceDaily. www.sciencedaily.com/releases/1998/07/980715083913.htm (accessed July 28, 2014).

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