4KBQ

Structure of the CHIP-TPR domain in complex with the Hsc70 Lid-Tail domains

Summary for 4KBQ

• Entry DOI: 10.2210/pdb4kbq/pdb
• Related: 2C2L 3LOF 3Q49 4KBO
• Descriptor: E3 ubiquitin-protein ligase CHIP, Heat shock cognate 71 kDa protein (3 entities in total)
• Functional Keywords: tpr, e3 ubiquitin ligase, hsc70, ligase-protein binding complex, ligase/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : Q9UNE7 P11142
• Total number of polymer chains: 4
• Total formula weight: 54615.60

Authors

Page, R.C.,Amick, J.,Nix, J.C.,Misra, S. (deposition date: 2013-04-23, release date: 2015-01-14, Last modification date: 2023-09-20)

Primary citation

Zhang, H.,Amick, J.,Chakravarti, R.,Santarriaga, S.,Schlanger, S.,McGlone, C.,Dare, M.,Nix, J.C.,Scaglione, K.M.,Stuehr, D.J.,Misra, S.,Page, R.C.
A Bipartite Interaction between Hsp70 and CHIP Regulates Ubiquitination of Chaperoned Client Proteins.
Structure, 23:472-482, 2015

PubMed Abstract: The ubiquitin ligase CHIP plays an important role in cytosolic protein quality control by ubiquitinating proteins chaperoned by Hsp70/Hsc70 and Hsp90, thereby targeting such substrate proteins for degradation. We present a 2.91 Å resolution structure of the tetratricopeptide repeat (TPR) domain of CHIP in complex with the α-helical lid subdomain and unstructured tail of Hsc70. Surprisingly, the CHIP-TPR interacts with determinants within both the Hsc70-lid subdomain and the C-terminal PTIEEVD motif of the tail, exhibiting an atypical mode of interaction between chaperones and TPR domains. We demonstrate that the interaction between CHIP and the Hsc70-lid subdomain is required for proper ubiquitination of Hsp70/Hsc70 or Hsp70/Hsc70-bound substrate proteins. Posttranslational modifications of the Hsc70 lid and tail disrupt key contacts with the CHIP-TPR and may regulate CHIP-mediated ubiquitination. Our study shows how CHIP docks onto Hsp70/Hsc70 and defines a bipartite mode of interaction between TPR domains and their binding partners.

PubMed: 25684577
DOI: 10.1016/j.str.2015.01.003

Experimental method

X-RAY DIFFRACTION (2.91 Å)