7RI3

Crystal structure of Albireti Toxin, a diphtheria toxin homolog, from Streptomyces albireticuli

7RI3 の概要

• エントリーDOI: 10.2210/pdb7ri3/pdb
• 関連するPDBエントリー: 7RB4
• 分子名称: Diphtheria_T domain-containing protein, TETRAETHYLENE GLYCOL, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: diphtheria toxin, dt, homolog, streptomyces albireticuli, toxin
• 由来する生物種: Streptomyces albireticuli
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 258471.70

構造登録者

Sugiman-Marangos, S.N.,Gill, S.K.,Melnyk, R.A. (登録日: 2021-07-19, 公開日: 2022-04-20, 最終更新日: 2024-10-16)

主引用文献

Sugiman-Marangos, S.N.,Gill, S.K.,Mansfield, M.J.,Orrell, K.E.,Doxey, A.C.,Melnyk, R.A.
Structures of distant diphtheria toxin homologs reveal functional determinants of an evolutionarily conserved toxin scaffold.
Commun Biol, 5:375-375, 2022

PubMed Abstract: Diphtheria toxin (DT) is the archetype for bacterial exotoxins implicated in human diseases and has played a central role in defining the field of toxinology since its discovery in 1888. Despite being one of the most extensively characterized bacterial toxins, the origins and evolutionary adaptation of DT to human hosts remain unknown. Here, we determined the first high-resolution structures of DT homologs outside of the Corynebacterium genus. DT homologs from Streptomyces albireticuli (17% identity to DT) and Seinonella peptonophila (20% identity to DT), despite showing no toxicity toward human cells, display significant structural similarities to DT sharing both the overall Y-shaped architecture of DT as well as the individual folds of each domain. Through a systematic investigation of individual domains, we show that the functional determinants of host range extend beyond an inability to bind cellular receptors; major differences in pH-induced pore-formation and cytosolic release further dictate the delivery of toxic catalytic moieties into cells, thus providing multiple mechanisms for a conserved structural fold to adapt to different hosts. Our work provides structural insights into the expanding DT family of toxins, and highlights key transitions required for host adaptation.

PubMed: 35440624
DOI: 10.1038/s42003-022-03333-9

実験手法

X-RAY DIFFRACTION (2.69 Å)