7RI3

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

Summary for 7RI3

• Entry DOI: 10.2210/pdb7ri3/pdb
• Related: 7RB4
• Descriptor: Diphtheria_T domain-containing protein, TETRAETHYLENE GLYCOL, ACETATE ION, ... (5 entities in total)
• Functional Keywords: diphtheria toxin, dt, homolog, streptomyces albireticuli, toxin
• Biological source: Streptomyces albireticuli
• Total number of polymer chains: 4
• Total formula weight: 258471.70

Authors

Sugiman-Marangos, S.N.,Gill, S.K.,Melnyk, R.A. (deposition date: 2021-07-19, release date: 2022-04-20, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.69 Å)