PDBsum entry 2oxq

Ligase

PDB id: 2oxq

Contents

Protein chains

149 a.a. *

72 a.a. *

Metals

_CL ×3

Waters ×4

* Residue conservation analysis

PDB id:

2oxq

Name:

Ligase

Title:

Structure of the ubch5 :chip u-box complex

Structure:

Ubiquitin-conjugating enzyme e2d 1. Chain: a, b. Fragment: ubch5. Synonym: ubc4/5 homolog, yeast. Engineered: yes. Stip1 homology and u-box containing protein 1. Chain: c, d. Fragment: u-box domain. Engineered: yes

Source:

Danio rerio. Zebrafish. Organism_taxid: 7955. Gene: ube2d1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: stub1.

Resolution:

2.90Å R-factor: 0.240 R-free: 0.272

Authors:

Z.Xu,J.C.Nix,K.I.Devlin,S.Misra

Key ref:

Z.Xu et al. (2008). Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes. Bmc Struct Biol, 8, 26-26. PubMed id: 18485199

Date:

20-Feb-07 Release date: 19-Feb-08

Protein chains

Q6PC58  (Q6PC58_DANRE) -  Ubiquitin-conjugating enzyme E2 D1 from Danio rerio

Seq: 147 a.a.

Struc: 149 a.a.

Protein chains

F6NGW2  (F6NGW2_DANRE) -  STIP1 homology and U box-containing protein 1 from Danio rerio

Seq: 284 a.a.

Struc: 72 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: Chains A, B: E.C.6.3.2.19 - Transferred entry: 2.3.2.23, 2.3.2.27 and 6.2.1.45.
• Reaction: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine
• Enzyme class 2: Chains C, D: 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

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

Bmc Struct Biol 8:26-26 (2008)

PubMed id: 18485199

Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes.

Z.Xu, E.Kohli, K.I.Devlin, M.Bold, J.C.Nix, S.Misra.

ABSTRACT

BACKGROUND: Ubiquitin (E3) ligases interact with specific ubiquitin conjugating (E2) enzymes to ubiquitinate particular substrate proteins. As the combination of E2 and E3 dictates the type and biological consequence of ubiquitination, it is important to understand the basis of specificity in E2:E3 interactions. The E3 ligase CHIP interacts with Hsp70 and Hsp90 and ubiquitinates client proteins that are chaperoned by these heat shock proteins. CHIP interacts with two types of E2 enzymes, UbcH5 and Ubc13-Uev1a. It is unclear, however, why CHIP binds these E2 enzymes rather than others, and whether CHIP interacts preferentially with UbcH5 or Ubc13-Uev1a, which form different types of polyubiquitin chains. RESULTS: The 2.9 A crystal structure of the CHIP U-box domain complexed with UbcH5a shows that CHIP binds to UbcH5 and Ubc13 through similar specificity determinants, including a key S-P-A motif on the E2 enzymes. The determinants make different relative contributions to the overall interactions between CHIP and the two E2 enzymes. CHIP undergoes auto-ubiquitination by UbcH5 but not by Ubc13-Uev1a. Instead, CHIP drives the formation of unanchored polyubiquitin by Ubc13-Uev1a. CHIP also interacts productively with the class III E2 enzyme Ube2e2, in which the UbcH5- and Ubc13-binding specificity determinants are highly conserved. CONCLUSION: The CHIP:UbcH5a structure emphasizes the importance of specificity determinants located on the long loops and central helix of the CHIP U-box, and on the N-terminal helix and loops L4 and L7 of its cognate E2 enzymes. The S-P-A motif and other specificity determinants define the set of cognate E2 enzymes for CHIP, which likely includes several Class III E2 enzymes. CHIP's interactions with UbcH5, Ube2e2 and Ubc13-Uev1a are consistent with the notion that Ubc13-Uev1a may work sequentially with other E2 enzymes to carry out K63-linked polyubiquitination of CHIP substrates.