PDBsum entry 4kbq

Ligase/protein binding

PDB id: 4kbq

Contents

Protein chains

130 a.a.

87 a.a.

91 a.a.

Waters ×52

PDB id:

4kbq

Name:

Ligase/protein binding

Title:

Structure of the chip-tpr domain in complex with the hsc70 lid-tail domains

Structure:

E3 ubiquitin-protein ligase chip. Chain: a, b. Fragment: tpr. Synonym: antigen ny-co-7, cll-associated antigen kw-8, carboxy terminus of hsp70-interacting protein, stip1 homology and u box- containing protein 1. Engineered: yes. Heat shock cognate 71 kda protein. Chain: d, c.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: chip, pp1131, stub1. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: hsc70, hsp73, hspa10, hspa8.

Resolution:

2.91Å R-factor: 0.227 R-free: 0.263

Authors:

R.C.Page,J.Amick,J.C.Nix,S.Misra

Key ref:

H.Zhang et al. (2015). A bipartite interaction between Hsp70 and CHIP regulates ubiquitination of chaperoned client proteins. Structure, 23, 472-482. PubMed id: 25684577 DOI: 10.1016/j.str.2015.01.003

Date:

23-Apr-13 Release date: 14-Jan-15

Protein chains

Q9UNE7  (CHIP_HUMAN) -  E3 ubiquitin-protein ligase CHIP from Homo sapiens

Seq: 303 a.a.

Struc: 130 a.a.

Protein chain

P11142  (HSP7C_HUMAN) -  Heat shock cognate 71 kDa protein from Homo sapiens

Seq: 646 a.a.

Struc: 87 a.a.*

Protein chain

P11142  (HSP7C_HUMAN) -  Heat shock cognate 71 kDa protein from Homo sapiens

Seq: 646 a.a.

Struc: 91 a.a.*

* PDB and UniProt seqs differ at 26 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chains A, B: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine
• Enzyme class 3: Chains D, C: E.C.3.6.4.10 - non-chaperonin molecular chaperone ATPase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.str.2015.01.003

Structure 23:472-482 (2015)

PubMed id: 25684577

A bipartite interaction between Hsp70 and CHIP regulates ubiquitination of chaperoned client proteins.

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.

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.