4.1.1. Hsp70

The 70 kDa heat shock protein (Hsp70) and its homologs heat shock cognate 70 (Hsc70) in the cytosol and BiP/GRP78 in the ER are some of the most abundant chaperones engaged in a plethora of folding and refolding processes. Hsp70 consists of two domains: an N-terminal nucleotide-binding domain (NBD) of ~40 kDa and a C-terminal substrate-binding domain (SBD) of ~30 kDa, connected by a hydrophobic linker. The Hsp70 cycle can use co-chaperones such as Hsp40 to recognize and transfer a substrate protein to Hsp70, J proteins to stimulate ATP hydrolysis in the SBD, and nuclear exchange factor proteins to change ATP to ADP in the NBD. ADP-Hsp70 holds a substrate protein in an unfolded state, until it has no exposed hydrophobic patches and spontaneous folding is achieved [60,69].
