Molecular chaperones are central to proteostasis, as they are involved not only in protein folding but also in degradation 2, 3. Interruption of this process contributes to a variety of pathologies including neurodegenerative disorders and cancer 1. Protein homeostasis, or proteostasis, is the delicate balance of synthesis, folding, trafficking, and degradation of intra- and extracellular proteins. These complexes are inherently flexible, which is important for the ubiquitination process.

The 3D structures of the two complexes, obtained using a combination of cryoelectron microscopy and crosslinking mass spectrometry, showed the substrate located between the chaperone and the cochaperone, suggesting a ubiquitination mechanism in which the chaperone-bound substrate is presented to CHIP. Both ternary complexes (Hsp70:p53-TMGST:CHIP and Hsp90:p53-TMGST:CHIP) ubiquitinated the substrate at a higher efficiency than in the absence of the chaperones. We generated complexes between the chaperones (Hsp70 or Hsp90), the cochaperone CHIP and, as substrate, a p53 variant containing the GST protein (p53-TMGST). This is the case for Hsp70 and Hsp90 which, in concert with the cochaperone CHIP, direct their bound substrate to degradation through ubiquitination. Some molecular chaperones are involved not only in assisting the folding of proteins but also, given appropriate conditions, in their degradation.

3d comic the chaperone episode 61