Function, Therapeutic Potential, and Inhibition of Hsp70 Chaperones

Hsp70s are among the most highly conserved proteins in all of biology. Through an iterative binding and release of exposed hydrophobic residues on client proteins, Hsp70s can prevent aggregation and promote folding to the native state of their client proteins. The human proteome contains eight canonical Hsp70s. Because Hsp70s are relatively promiscuous they play a role in folding a large proportion of the proteome. Hsp70s are implicated in disease through their ability to regulate protein homeostasis. In recent years, researchers have attempted to develop selective inhibitors of Hsp70 isoforms to better understand the role of individual isoforms in biology and as potential therapeutics. Selective inhibitors have come from rational design, forced localization, and serendipity, but the development of completely selective inhibitors remains elusive. In the present review, we discuss the Hsp70 structure and function, the known Hsp70 client proteins, the role of Hsp70s in disease, and current efforts to discover Hsp70 modulators.

Automated summary

Hsp70s are highly conserved proteins that prevent aggregation and promote folding of client proteins through binding and releasing exposed hydrophobic residues. Due to their promiscuity, they play a crucial role in folding a large proportion of the proteome and are implicated in disease through regulating protein homeostasis. Efforts are being made to develop selective inhibitors of Hsp70 isoforms to understand their role in biology and potentially treat diseases.