4ZQW

CdiI from Escherichia coli EC869 in complex with a macrocyclic peptide

4ZQW の概要

• エントリーDOI: 10.2210/pdb4zqw/pdb
• 関連するBIRD辞書のPRD_ID: PRD_002182
• 分子名称: Immunity protein CdiI-o11, macrocyclic peptide, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: immunity, macrocycle, toxin, toxin-inhibitor complex, toxin/inhibitor
• 由来する生物種: Escherichia coli O157:H7 (strain EC869); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 43487.93

構造登録者

Morse, R.P.,Goulding, C.W. (登録日: 2015-05-11, 公開日: 2015-10-28, 最終更新日: 2023-12-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.001 Å)