![]() "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. When these chaperones were added to the aggregated luciferase together with Hsp104, there was a profound increase in the amount of recovered functional protein. Lindquist and Glover pinpointed two heat shock proteins that were observed to interact with Hsp104-Hsp40 and Hsp70. However, when other heat shock proteins from yeast were added, reactivation of luciferase was observed. They found that Hsp104 alone could not untangle the clusters. To find out where and how Hsp104 works, the researchers tested its ability to prevent aggregation and promote refolding of heat denatured firefly luciferase. This ability is essential to the survival of cells facing extreme heat." But now we have shown that at least one heat shock protein, namely Hsp104, has the ability to rescue proteins that have already aggregated. "We thought that Hsps bind to sticky surfaces presented by denatured proteins to prevent them from interacting and forming a blob-and they do. "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 Molecular Genetics and Cell Biology. 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. When exposed to sudden shifts in temperature, all organisms make heat shock proteins, otherwise known as chaperones, which protect (to some extent) against denaturation. In the body, heat stress can do the same thing to proteins, making them dysfunctional. 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). 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. But now, Susan Lindquist, PhD, and colleague John Glover, PhD, have shown that protein snarls can actually be rescued by Hsp104 with the assistance of two other heat shock proteins. Previously, scientists thought Hsps could only prevent proteins from aggregating as temperatures rise. Researchers from the Howard Hughes Medical Institute at the University of Chicago report in the Jissue 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. Denatured proteins rescued by trio of chaperones
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |