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A Bipartite Interaction between Hsp70 and CHIP Regulates Ubiquitination of Chaperoned Client Proteins
Author(s) -
Page Richard,
Zhang Huaqun,
McGlone Cameron
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.883.2
Subject(s) - ubiquitin , ubiquitin ligase , hsp70 , microbiology and biotechnology , chaperone (clinical) , cytosol , hsp90 , biology , chip , heat shock protein , biochemistry , enzyme , computer science , gene , telecommunications , medicine , pathology
The ubiquitin ligase CHIP plays an important role in cytosolic protein quality control by ubiquitinating proteins chaperoned by Hsp70/Hsc70 and Hsp90 and targeting them for degradation. We present a 2.91 Å resolution structure of the 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 GPTIEEVD motif of the tail, exhibiting a novel mode of chaperone‐TPR domain interaction. 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. Post‐translational modification 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 new bipartite smode of interaction between TPR domains and their binding partners.