One domain fits all: Using disordered regions to sequester misfolded proteins

Abstract

Small heat shock proteins (sHsps) are adenosine triphosphate-independent chaperones that protect cells from misfolded proteins. In this issue, Grousl et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201708116) show that the yeast sHsp Hsp42 uses a prion-like intrinsically disordered domain to bind and sequester misfolded proteins in protein deposition sites.

Figure 1.

Effects of domain deletions in Hsp42. WT Hsp42 (green) efficiently sequesters misfolded proteins in one or two CytoQ sites in the cytoplasm. In vitro, it is active as a chaperone and as an aggregase and sustains cellular fitness during stress. The ΔPrLD mutant (orange) lacks the substrate-binding site and thus fails to act as a chaperone or an aggregase in vitro and in vivo. As a consequence, the cells show decreased fitness. Deletion of the IDD in the ΔIDD mutant (blue) results in increased chaperone and aggregase activity and increased CytoQ formation in vivo. However, cellular fitness is similarly impaired in this mutant, presumably because the formed aggregates have different material properties. ACD-CTE, ACD and C-terminal extension domain.