Figure 4.

Hsp70s hand off substrates to downstream chaperones, like Hsp90s. The action of the Hsp70 on substrates influences them so that they interact productively with the partner chaperone. Here the example of the glucocorticoid receptor ligand-binding domain (GR-LBD) is illustrated. As described in the text, the conformational ensemble of the GR-LBD contains locally unfolded states with an exposed Hsp70 binding site (cyan). The binding of the Hsp70 selects these conformations, which are in turn delivered in a process facilitated by co-chaperones Hop and p23 to the Hsp90 for further maturation steps. The coloring scheme is as in Figure 2.