(A) Schematic representation of the structural domains of Hsp70s. The sequence numbers are based on the E. coli Hsp70, DnaK. Structures of DnaK showing (B) the canonical ADP-bound undocked state (PDB ID 2kho [12]), and (C) the canonical ATP-bound docked state (PDB ID 4b9q [17]). The NBD is colored in blue. In the substrate-binding domain (SBD), the βSBD is colored green, α-lid in red, and the linker in orange. The bound nucleotide and the peptide substrate NRLLLTG are shown in purple. (D) Subdomain organization of the NBD of a representative Hsp70. The structure shown is ADP-bound Hsc70 (PDB ID 3hsc [92]). Subdomains IA, IB, IIA, and IIB are colored in yellow, green, blue, and red, respectively. The crossing α-helices are shown in cyan. (E) Structure of the DnaK SBD bound to the peptide NRLLLTG (PDB 1dkz [39]). The binding mode of peptide substrate is illustrated in Figure 7.