Endoplasmic reticulum protein quality control is determined by cooperative interactions between Hsp/c70 protein and the CHIP E3 ligase

Background: The CHIP E3 ligase regulates Hsp70 pro-degradation activities. Results: The P269A CHIP U-box mutation induces CHIP oligomerization and modulates nucleotide- and substrate-dependent interactions between the TPR domain and Hsp70 C terminus. Conclusion: The U-box domain plays a key role in CHIP recruitment to Hsp70-client complexes, possibly by controlling oligomerization. Significance: Hsp70-CHIP substrate triage is governed by complex allosteric interactions between multiple domains in both proteins.