4ZQU

CdiA-CT/CdiI toxin and immunity complex from Yersinia pseudotuberculosis

Summary for 4ZQU

• Entry DOI: 10.2210/pdb4zqu/pdb
• Descriptor: CdiA-CT toxin, Conserved domain protein, CdiI toxin, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: toxin, immunity, complex, endonuclease
• Biological source: Yersinia pseudotuberculosis serotype O:3 (strain YPIII); More
• Total number of polymer chains: 2
• Total formula weight: 34787.38

Authors

Morse, R.P.,Johnson, P.M.,Credali, A.,Goulding, C.W. (deposition date: 2015-05-11, release date: 2015-10-28, Last modification date: 2023-09-27)

Primary citation

Morse, R.P.,Willett, J.L.,Johnson, P.M.,Zheng, J.,Credali, A.,Iniguez, A.,Nowick, J.S.,Hayes, C.S.,Goulding, C.W.
Diversification of beta-Augmentation Interactions between CDI Toxin/Immunity Proteins.
J.Mol.Biol., 427:3766-3784, 2015

PubMed 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.

PubMed: 26449640
DOI: 10.1016/j.jmb.2015.09.020

Experimental method

X-RAY DIFFRACTION (2.09 Å)