biostudies-literatureCiesielski SJNational Institute of General Medical SciencesNIGMS NIH HHSNational Science Center, Poland1465-1477https://www.ebi.ac.uk/biostudies/studies/S-EPMC11209805biostudies-literatureUnknown598(12)J-domain proteins are critical Hsp70 co-chaperones. A and B types have a poorly understood glycine-rich region (G_rich) adjacent to their N-terminal J-domain (J_dom). We analyzed the ability of J_dom/G_rich 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 G_rich 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 G_rich-Hsp70 interaction of Classes A and B J-domain proteins can fine tune the activity of Hsp70, thus beFEBS lettersComparative structural and functional analysis of the glycine-rich regions of Class A and B J-domain protein cochaperones of Hsp70.PMC11209805R35 GM127009OPUS 21 2021/41/B/NZ8/02835P41 GM136463Stolarska MSchilke BATonelli MCiesielski SJTomiczek BCraig EAfalseComparative structural and functional analysis of the glycine-rich regions of Class A and B J-domain protein cochaperones of Hsp70.J-domain proteins are critical Hsp70 co-chaperones. A and B types have a poorly understood glycine-rich region (G_rich) adjacent to their N-terminal J-domain (J_dom). We analyzed the ability of J_dom/G_rich 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 G_rich 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 G_rich-Hsp70 interaction of Classes A and B J-domain proteins can fine tune the activity of Hsp70, thus be2024-01-01T00:00:00Z2024 Jun2026-06-03T07:33:15.075Z2026-04-26T03:09:44.433ZS-EPMC112098053852966310.1002/1873-3468.14857