Multiple functionalities of molecular chaperones revealed through systematic mapping of their interaction networks.

Chaperones are a highly interactive group of proteins that function globally in many cellular processes involved in maintaining protein homeostasis. Traditional biochemical assays typically do not provide a complete view of the intricate networks through which chaperones collaborate to promote proteostasis. Recent advances in high-throughput systematic analyses of chaperone interactions have uncovered that chaperones display a remarkable cooperativity in their interactions with numerous client proteins. This cooperativity has been found to be a fundamental aspect of a properly functioning cell. Aberrant formation or improper regulation of these interactions can easily lead to disease states. Herein, we provide an overview of the use of large-scale interaction assays, whether physical (protein-protein) or genetic (epistatic), to study chaperone interaction networks. Importantly, we discuss the ongoing need for such studies to determine the mechanisms by which protein homeostasis is controlled in the cell.