PDBsum entry 3cvr

Ligase

PDB id: 3cvr

Contents

Protein chain

477 a.a. *

Waters ×39

* Residue conservation analysis

PDB id:

3cvr

Name:

Ligase

Title:

Crystal structure of the full length ipah3

Structure:

Invasion plasmid antigen. Chain: a. Synonym: ubiquitin e3 ligase. Engineered: yes

Source:

Shigella flexneri 2a. Organism_taxid: 198214. Strain: 301. Gene: ipah_3. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

2.80Å R-factor: 0.252 R-free: 0.277

Authors:

Y.Zhu,F.Shao

Key ref:

Y.Zhu et al. (2008). Structure of a Shigella effector reveals a new class of ubiquitin ligases. Nat Struct Biol, 15, 1302-1308. PubMed id: 18997779 DOI: 10.1038/nsmb.1517

Date:

19-Apr-08 Release date: 11-Nov-08

Protein chain

Q83RJ4  (IPA3_SHIFL) -  E3 ubiquitin-protein ligase ipaH3 from Shigella flexneri

Seq: 571 a.a.

Struc: 477 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: 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

DOI no: 10.1038/nsmb.1517

Nat Struct Biol 15:1302-1308 (2008)

PubMed id: 18997779

Structure of a Shigella effector reveals a new class of ubiquitin ligases.

Y.Zhu, H.Li, L.Hu, J.Wang, Y.Zhou, Z.Pang, L.Liu, F.Shao.

ABSTRACT

Bacterial pathogens have evolved effector proteins with ubiquitin E3 ligase activities through structural mimicking. Here we report the crystal structure of the Shigella flexneri type III effector IpaH3, a member of the leucine-rich repeat (LRR)-containing bacterial E3 family. The LRR domain is structurally similar to Yersinia pestis YopM and potentially binds to substrates. The structure of the C-terminal E3 domain differs from the typical RING- and HECT-type E3s. IpaH3 synthesizes a Lys48-linked ubiquitin chain, and the reaction requires noncovalent binding between ubiquitin and a specific E2, UbcH5. Free ubiquitin serves as an acceptor for IpaH3-catalyzed ubiquitin transfer. Cys363 within a conserved CXD motif acts as a nucleophile to catalyze ubiquitin transfer through a transthiolation reaction. The D365N mutant is devoid of E3 activities but turns into a potent ubiquitin-E2 thioesterase. Our analysis establishes a structurally and mechanistically distinct class of ubiquitin ligases found exclusively in pathogenic or symbiotic bacteria.

Selected figure(s)

Figure 2.
(a) Stereo view of the overall structure of full-length IpaH3. The structure consists of two domains: the N-terminal leucine-rich repeat (LRR) domain (gold) and the C-terminal helical domain (green) with the E3 ligase activity. Secondary structures are marked with numbered labels, and broken lines indicate disordered loop regions. (b) Secondary-structure organization and amino acid compositions of the nine LRR motifs in IpaH3. Secondary-structural elements are depicted along and above the sequence. The consensus sequences of LRR1–LRR7 are highlighted in green and the YopM sequence is listed underneath for comparison. (c) Backbone superimposition of the structures of YopM (blue; PDB 1JL5) and the LRR domain of IpaH3 (gold).

Figure 3.
(a) Structure of the C-terminal E3 ligase domain of IpaH3. Secondary structures are marked with numbered labels, and broken lines indicate disordered loop regions. Cys363 and Asp365, which are important for catalyzing ubiquitin transfer, are highlighted in yellow and shown in sticks. (b) Representative structures of RING-finger and U-box E3 ligases. The RING-finger and U-box domains were selected from RING-type E3 ligase Cbl (PDB 1FBV) and U-box E3 ligase Ufd2p (PDB 2QIZ), respectively. The zinc ions in Cbl are colored orange. (c) Structure of the HECT domain of E6AP (PDB 1D5F). The N and C lobes are colored red and purple, respectively. The catalytic cysteine (Cys820) and the hinge loop connecting the two lobes are indicated.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2008, 15, 1302-1308) copyright 2008.

Figures were selected by an automated process.