Complex Multigene Family of Functionally Distinct Hsp70s of Yeast

The highly conserved 70-kD heat shock proteins (Hsp70s) comprise the central core of a chaperone system for protein translocation across membranes and protein folding (for reviews, see Craig et al. 1993; Georgopoulos and Welch 1993; Hendrick and Hartl 1993; Langer and Neupert 1994). This chaperone activity relies on the ability of Hsp70s to transiently interact with nonnative protein substrates. The cycle of binding and release of substrate proteins is thus a crucial aspect of the mechanism of Hsp70 activity. Adenine nucleotides play a critical role in this binding/release cycle (McKay et al. 1994). All Hsp70s analyzed bind adenine nucleotide in the highly conserved amino-terminal domain. The structure of this nucleotide-binding domain has been determined for the Hsc70 protein from bovine brain (Flaherty et al. 1990) and determined to be similar to G actin and the nucleotide-binding sites of hexokinase and glycerol kinase (Flaherty et al. 1990). All Hsp70s also possess...