Structure of the ATPase fragment of a 70K heat-shock cognate protein.

(a) The Hsp70s schematic domains. The Hsp70s consist of two high conserved functional domains including an NBD and a C‐terminal substrate‐binding domain (SBD), also an EEVD‐motif at C‐terminal. The NBD contains the ATP/ADP pocket that binds and The SBD contains a substrate‐binding pocket that interacts with extended polypeptides as substrate, an α‐helical subdomain from the C‐terminal side of SBD forms a flexible lid. EEVD‐motif participates in binding to co‐chaperones and other HSPs. (b) the complete amino acid sequence of human Hsp70 (UniProtKB identifier: P0DMV8) as a major stress‐inducible member of the Hsp70 family. (c) Secondary structures of Hsp70 virtualized using VMD 1.9.1 software. Hsp70, heat shock protein 70 kDa; NBD, N‐terminal nucleotide‐binding domain; SBD, substrate binding domain at C‐terminal.

The function of Hsp70 in both (re) folding and degradation of misfolded client protein. (a) Schematic of the Hsp70 ATP–ADP cycle for (re) folding of client protein which causes a conformational change of the chaperone, ATP hydrolysis, and exchange. (b) Hsp70–CHIP complex that promotes client protein ubiquitination and proteasomal degradation. CHIP interacts with the TPR domain of Hsp70 and acts as a ubiquitin ligase for clients. CHIP, chromatin immunoprecipitation; Hsp70, heat shock protein 70 kDa; TPR,

1j3s: Solution Structure of Reduced Recombinant Human Cytochrome c