Heat-shock proteins have unrecognized roles in cells

When a biological cell is under duress, a family of heat-shock proteins called Hsp70 steps in to help unfolded peptide chains refold into functional proteins. The same family also helps prefolded peptide chains find a correct three-dimensional conformation in cells. But Hsp70s have a lot more tricks up their sleeves, according to a team led by Sander J. Tans of Fundamental Research on Matter’s Institute for Atomic & Molecular Physics (Nature 2016, DOI: 10.1038/nature20137).

The researchers have found that Hsp70s also bind mature, folded proteins and interact with intermediates in folding processes, which “suggests that Hsp70s play a bigger part in protein homeostasis than was thought,” comment Qinglian Liu of Virginia Commonwealth University and Elizabeth A. Craig of the University of Wisconsin, Madison, in an associated Nature commentary (DOI: 10.1038/nature20470). For example, Hsp70s bind protein receptors and kinases, whose structure and conformation can change as part of their job in the cell. This suggests Hsp70s may play a role in regulation of basic cellular processes—instead of just being cellular paramedics.

Tans tells C&EN that it’s been difficult to determine the full functional potential of the Hsp70 family because some of the protein structures it interacts with are transient in the cell and thus hard to observe. So Tans’s team used optical tweezers to modify the conformations of single proteins and then see how Hsp70s responded. In doing so, the researchers found that Hsp70s’ repertoire is much broader than previously thought.