Modulation of Hsp70 Interactions with Co‐chaperones via Phosphorylation

• DOI: 10.1096/fasebj.29.1_supplement.713.1
• Publication Date: 2021-06-21T18:45:18Z
• Authors: Huaqun Zhang; Cameron McGlone; Kathleen George; Katherine Makaroff; Kelsey Cottingim; Jay Nix; Jonathan Schisler; Richard Page
• Keywords: C-terminus; Chaperone (clinical)

The C-terminus of the 70-kilodalton heat shock protein interacts with TPR domains within ubiquitin ligase CHIP (C-terminus Hsp70 interacting protein) and Hop (Hsp70-Hsp90 organizing protein). Interactions allow for formation a productive encounter complex that facilitates ubiquitination Hsp70-bound substrates, thereby targeting those proteins proteasomal degradation. In contrast, interaction coordinates active refolding in concert Hop-recruited Hsp90. Phosphorylation causes switch from preferential binding to by Hsp70. Here we show minor structural differences between result substantial both phosphorylated nonphosphorylated C-terminal peptides. Our biophysical data also identify role compensatory mutations may function reverse this preference shift back CHIP.