Mechanisms of Chaperones and their Networks

Molecular chaperones and degradation enzymes, which are responsible for cellular protein homeostasis, work in networks and teams. Several faculty members in the Protein Homeostasis group investigate the detailed biochemical mechanisms of chaperones and degradation enzymes, providing insight into their potential as drug targets, and the networks in which any of these components work. For example, in-depth studies are underway on the allosteric mechanism of Hsp70s, including efforts to deduce activities and mechanisms that are unique to particular Hsp70s and might be exploited to achieve specificity of small molecule modulators (Gierasch). Similarly, the detailed biochemical and biophysical basis for small heat shock protein functions is being elucidated in the Vierling lab, and the Hebert lab is dissecting functions of individual components of the ER quality control machinery.

Most excitingly, however, will be the ongoing work to integrate chaperone functions in networks and teams. Both the Chien and Vierling labs examine partnerships of chaperones and proteases that determine protein fate—either refolding or degradation. The Hebert lab, together with the Gierasch and Gershenson labs, is reconstituting the quality control system in the ER lumen, where several different chaperones collaborate.