Comparative structural and functional analysis of the glycine‐rich regions of Class A and B J‐domain protein cochaperones of Hsp70

Abstract

J‐domain proteins are critical Hsp70 co‐chaperones. A and B types have a poorly understood glycine‐rich region (Grich) adjacent to their N‐terminal J‐domain (Jdom). We analyzed the ability of Jdom/Grich segments of yeast Class B Sis1 and a suppressor variant of Class A, Ydj1, to rescue the inviability of sis1‐∆. In each, we identified a cluster of Grich residues required for rescue. Both contain conserved hydrophobic and acidic residues and are predicted to form helices. While, as expected, the Sis1 segment docks on its J‐domain, that of Ydj1 does not. However, data suggest both interact with Hsp70. We speculate that the Grich–Hsp70 interaction of Classes A and B J‐domain proteins can fine tune the activity of Hsp70, thus being particularly important for the function of Class B.