The chaperone Hsp70 lives up to its name, guiding its partner Hsp100 into position in two different situations, Winkler et al. reveal.
Stress can spur proteins to misfold and clump. Hsp70 and Hsp100 enable yeast, bacteria, and plants to restore and reuse aggregated proteins. These chaperones collaborate to pluck proteins from aggregates and feed them through a channel in Hsp100, after which the proteins can refold into their normal shapes. In yeast, the chaperone duo also helps prions spread. Unlike the disease-causing prions of humans, some yeast prions seem to be beneficial, boosting resistance to toxins, for instance. Working together, the chaperones chop prion fibrils into smaller segments that can move into the daughter cell during division. However, researchers haven't nailed down Hsp70’s role during these two processes.
Winkler et al. found that Hsp70 helps direct Hsp100 to clusters of misshapen proteins. For example, the researchers tracked the chaperones in E. coli cells that were lacking either ClpB (the bacterial Hsp100) or DnaK (the bacterial equivalent of Hsp70). When DnaK was absent, ClpB rarely found its target. But DnaK could still locate and stick to protein aggregates even in the absence of ClpB. The researchers showed that these results also held true for yeast.
The team discovered that the two chaperones have the same relationship during the dismemberment of prion fibrils, with the yeast version of Hsp70 ushering its partner into place. The researchers note that vertebrates don't have an equivalent of Hsp100, but the results suggest that their version of Hsp70 could have a role in prion transmission and pathogenesis.