PDBsum entry 4jqu

Ligase/protein binding

PDB id: 4jqu

Contents

Protein chains

163 a.a.

54 a.a.

Ligands

BTB

PEG ×2

Waters ×136

PDB id:

4jqu

Name:

Ligase/protein binding

Title:

Crystal structure of ubc7p in complex with the u7br of cue1p

Structure:

Ubiquitin-conjugating enzyme e2 7. Chain: a. Synonym: ubc7p, ubiquitin carrier protein, ubiquitin-conjugating enzyme e2-18 kda, ubiquitin-protein ligase. Engineered: yes. Coupling of ubiquitin conjugation to er degradation protein 1. Chain: b. Fragment: u7br (unp residues 151-203).

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 559292. Strain: atcc 204508 / s288c. Gene: qri8, ubc7, ubc7p, ym9711.12, ymr022w. Expressed in: escherichia coli. Expression_system_taxid: 511693. Gene: cue1, cue1p, kis4, ym8156.06, ymr264w.

Resolution:

1.81Å R-factor: 0.186 R-free: 0.225

Authors:

Y.-H.Liang,M.B.Metzger,A.M.Weissman,X.Ji

Key ref:

M.B.Metzger et al. (2013). A structurally unique E2-binding domain activates ubiquitination by the ERAD E2, Ubc7p, through multiple mechanisms. Mol Cell, 50, 516-527. PubMed id: 23665230 DOI: 10.1016/j.molcel.2013.04.004

Date:

20-Mar-13 Release date: 29-May-13

Protein chain

Q02159  (UBC7_YEAST) -  Ubiquitin-conjugating enzyme E2 7 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 165 a.a.

Struc: 163 a.a.*

Protein chain

P38428  (CUE1_YEAST) -  Coupling of ubiquitin conjugation to ER degradation protein 1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 203 a.a.

Struc: 54 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: E.C.2.3.2.23 - E2 ubiquitin-conjugating enzyme.
• Reaction: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L- cysteine

DOI no: 10.1016/j.molcel.2013.04.004

Mol Cell 50:516-527 (2013)

PubMed id: 23665230

A structurally unique E2-binding domain activates ubiquitination by the ERAD E2, Ubc7p, through multiple mechanisms.

M.B.Metzger, Y.H.Liang, R.Das, J.Mariano, S.Li, J.Li, Z.Kostova, R.A.Byrd, X.Ji, A.M.Weissman.

ABSTRACT

Cue1p is an integral component of yeast endoplasmic reticulum (ER)-associated degradation (ERAD) ubiquitin ligase (E3) complexes. It tethers the ERAD ubiquitin-conjugating enzyme (E2), Ubc7p, to the ER and prevents its degradation, and also activates Ubc7p via unknown mechanisms. We have now determined the crystal structure of the Ubc7p-binding region (U7BR) of Cue1p with Ubc7p. The U7BR is a unique E2-binding domain that includes three α-helices that interact extensively with the "backside" of Ubc7p. Residues essential for E2 binding are also required for activation of Ubc7p and for ERAD. We establish that the U7BR stimulates both RING-independent and RING-dependent ubiquitin transfer from Ubc7p. Moreover, the U7BR enhances ubiquitin-activating enzyme (E1)-mediated charging of Ubc7p with ubiquitin. This demonstrates that an essential component of E3 complexes can simultaneously bind to E2 and enhance its loading with ubiquitin. These findings provide mechanistic insights into how ubiquitination can be stimulated.