PDBsum entry 4zqw

Toxin/inhibitor

PDB id: 4zqw

Contents

Protein chains

167 a.a.

13 a.a.

Metals

_CL ×2

Waters ×132

PDB id:

4zqw

Name:

Toxin/inhibitor

Title:

Cdii from escherichia coli ec869 in complex with a macrocyclic peptide

Structure:

Immunity protein cdii-o11. Chain: b, d. Engineered: yes. Macrocyclic peptide. Chain: a, c. Engineered: yes

Source:

Escherichia coli o157:h7 (strain ec869). Organism_taxid: 478008. Strain: ec869. Gene: cdii4, cdiio11, ech7ec869_5884. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Escherichia coli. Organism_taxid: 562

Resolution:

2.00Å R-factor: 0.188 R-free: 0.231

Authors:

R.P.Morse,C.W.Goulding

Key ref:

R.P.Morse et al. (2015). Diversification of β-Augmentation Interactions between CDI Toxin/Immunity Proteins. J Mol Biol, 427, 3766-3784. PubMed id: 26449640 DOI: 10.1016/j.jmb.2015.09.020

Date:

11-May-15 Release date: 28-Oct-15

Protein chains

B3BM81  (CDII4_ECO5C) -  Immunity protein CdiI-o11 from Escherichia coli O157:H7 (strain EC869)

Seq: 167 a.a.

Struc: 167 a.a.

Protein chains

B3BM80  (CDIA4_ECO5C) -  Deoxyribonuclease CdiA-o11 from Escherichia coli O157:H7 (strain EC869)

Seq: 377 a.a.

Struc: 13 a.a.*

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

Enzyme reactions

• Enzyme class: Chains A, C: E.C.3.1.-.-

DOI no: 10.1016/j.jmb.2015.09.020

J Mol Biol 427:3766-3784 (2015)

PubMed id: 26449640

Diversification of β-Augmentation Interactions between CDI Toxin/Immunity Proteins.

R.P.Morse, J.L.Willett, P.M.Johnson, J.Zheng, A.Credali, A.Iniguez, J.S.Nowick, C.S.Hayes, C.W.Goulding.

ABSTRACT

Contact-dependent growth inhibition (CDI) is a widespread mechanism of inter-bacterial competition mediated by the CdiB/CdiA family of two-partner secretion proteins. CdiA effectors carry diverse C-terminal toxin domains (CdiA-CT), which are delivered into neighboring target cells to inhibit growth. CDI(+) bacteria also produce CdiI immunity proteins that bind specifically to cognate CdiA-CT toxins and protect the cell from auto-inhibition. Here, we compare the structures of homologous CdiA-CT/CdiI complexes from Escherichia coli EC869 and Yersinia pseudotuberculosis YPIII to explore the evolution of CDI toxin/immunity protein interactions. Both complexes share an unusual β-augmentation interaction, in which the toxin domain extends a β-hairpin into the immunity protein to complete a six-stranded anti-parallel sheet. However, the specific contacts differ substantially between the two complexes. The EC869 β-hairpin interacts mainly through direct H-bond and ion-pair interactions, whereas the YPIII β-hairpin pocket contains more hydrophobic contacts and a network of bridging water molecules. In accord with these differences, we find that each CdiI protein only protects target bacteria from its cognate CdiA-CT toxin. The compact β-hairpin binding pocket within the immunity protein represents a tractable system for the rationale design of small molecules to block CdiA-CT/CdiI complex formation. We synthesized a macrocyclic peptide mimic of the β-hairpin from EC869 toxin and solved its structure in complex with cognate immunity protein. These latter studies suggest that small molecules could potentially be used to disrupt CDI toxin/immunity complexes.