PDBsum entry 4zqu

Toxin

PDB id: 4zqu

Contents

Protein chains

124 a.a.

174 a.a.

Metals

_CL ×2

Waters ×148

PDB id:

4zqu

Name:

Toxin

Title:

Cdia-ct/cdii toxin and immunity complex from yersinia pseudotuberculosis

Structure:

Cdia-ct toxin, conserved domain protein. Chain: a. Engineered: yes. Cdii toxin. Chain: b. Engineered: yes

Source:

Yersinia pseudotuberculosis serotype o:3 (strain ypiii). Organism_taxid: 502800. Strain: ypiii. Gene: ypk_0575. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Salmonella enterica subsp. Enterica serovar rubislaw str. Atcc 10717.

Resolution:

2.09Å R-factor: 0.211 R-free: 0.257

Authors:

R.P.Morse,P.M.Johnson,A.Credali,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 chain

A0A0H3B0B8  (CDIA_YERPY) -  Deoxyribonuclease CdiA from Yersinia pseudotuberculosis serotype O:3 (strain YPIII)

Seq: 1077 a.a.

Struc: 124 a.a.

Protein chain

A0A0R4I987  (CDII_YERPY) -  Immunity protein CdiI-YPIII from Yersinia pseudotuberculosis serotype O:3 (strain YPIII)

Seq: 177 a.a.

Struc: 174 a.a.

Enzyme reactions

• Enzyme class: Chain A: 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.