UMass Amherst Study Demonstrates ‘Tunability’ of a Molecular Chaperone

For decades, molecular biologists studying a class of molecular chaperones known as heat shock proteins (Hsp70s) have relied on the Hsp70s found in bacteria as the model system. Now one of the world’s experts on the molecule and her team report that their investigation into whether Hsps from mammalian cells behave like those in bacteria reveals “key evolutionary variations” between them.

Lila Gierasch, an expert on Hsp70s at the University of Massachusetts Amherst, with her research team, report that Hsp70s from mammalian cells behave quite differently from bacterial Hsp70s. Because of the important roles Hsp70s play in protein misfolding diseases such as cancer and neurodegenerative diseases, the new findings “will have a major impact on how we think about Hsp70s,” she says.

Details of this work funded by the NIH’s Maximizing Investigators’ Research Awards program appear this month in Proceedings of the National Academy of Sciences. Gierasch’s co-authors include postdoctoral researcher Wenli Meng, research assistant professor Eugenia Clerico and an undergraduate, Natalie McArthur, now a graduate student at Columbia.

Gierasch explains that the versatile chaperone molecules, known as universal tools of cellular protein folding, interact with many different types of protein and are involved in many cellular functions. Hsp70s help proteins to fold, to translocate across membranes, to assemble into complexes, to be targeted for degradation, and to avoid harmful misfolding and aggregation. They are thought of as hubs in the cell’s finely balanced protein quality control network for good reason, she notes.

“If you want to cure cancer you might want to inhibit Hsp70s,” she notes, “but if you want a therapy for Alzheimer’s, which is a protein-folding disease, you want to activate them. Our new deeper understanding of the eukaryotic Hsp70s may offer a route to modulating them with more specificity. It may give us the ability to isolate and regulate a particular function.”

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Lila Gierasch