7RB4

Crystal structure of Peptono Toxin, a diphtheria toxin homolog, from Seinonella peptonophila

7RB4 の概要

• エントリーDOI: 10.2210/pdb7rb4/pdb
• 分子名称: Diphtheria toxin, C domain, IODIDE ION (3 entities in total)
• 機能のキーワード: diphtheria toxin, dt, homolog, seinonella peptonophila, toxin
• 由来する生物種: Seinonella peptonophila
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 70744.81

構造登録者

Sugiman-Marangos, S.N.,Gill, S.K.,Melnyk, R.A. (登録日: 2021-07-05, 公開日: 2022-04-20, 最終更新日: 2024-10-09)

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 (2.19 Å)