 |
PDBsum entry 4kbq
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Ligase/protein binding
|
PDB id
|
|
|
|
4kbq
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
A bipartite interaction between hsp70 and chip regulates ubiquitination of chaperoned client proteins.
|
|
|
Authors
|
|
H.Zhang,
J.Amick,
R.Chakravarti,
S.Santarriaga,
S.Schlanger,
C.Mcglone,
M.Dare,
J.C.Nix,
K.M.Scaglione,
D.J.Stuehr,
S.Misra,
R.C.Page.
|
|
|
Ref.
|
|
Structure, 2015,
23,
472-482.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
