UCSF

Molecular chaperones bind to misfolded proteins (“clients”) to protect them from aggregation and promote their folding. The following Chapters all focus on understanding how the protein-protein interactions (PPIs) between members of the molecular chaperone network and their client proteins regulate these processes. Specifically, I develop a functional genomic approach to explore which molecular chaperones are required for the stability of specific client proteins (Chapter 2) and use biophysical and biochemical approaches to probe how conserved amino acid sequences in the heat shock protein 70 (Hsp70) chaperone allow it to engage with two different classes of co-chaperones (Chapter 3). Together, these studies and recent literature reports suggest that weak interactions (i.e. micromolar) are critical to the molecular logic of chaperone-mediated folding.