PDBsum entry 4zqv

Immune system

PDB id: 4zqv

Contents

Protein chain

165 a.a.

Waters ×130

PDB id:

4zqv

Name:

Immune system

Title:

Cdii immunity protein from yersinia kristensenii

Structure:

Cdii immunity protein. Chain: a. Engineered: yes

Source:

Yersinia kristensenii atcc 33638. Organism_taxid: 527012. Gene: ykris0001_10740. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008

Resolution:

1.80Å R-factor: 0.185 R-free: 0.221

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 chain

C4TS51  (C4TS51_YERKR) -

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.