Common architecture of Tc toxins from human and insect pathogenic bacteria.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
10
04
2019
accepted:
18
09
2019
entrez:
31
10
2019
pubmed:
31
10
2019
medline:
22
5
2020
Statut:
epublish
Résumé
Tc toxins use a syringe-like mechanism to penetrate the membrane and translocate toxic enzymes into the host cytosol. They are composed of three components: TcA, TcB, and TcC. Low-resolution structures of TcAs from different bacteria suggest a considerable difference in their architecture and possibly in their mechanism of action. Here, we present high-resolution structures of five TcAs from insect and human pathogens, which show a similar overall composition and domain organization. Essential structural features, including a trefoil protein knot, are present in all TcAs, suggesting a common mechanism of action. All TcAs form functional pores and can be combined with TcB-TcC subunits from other species to form active chimeric holotoxins. We identified a conserved ionic pair that stabilizes the shell, likely operating as a strong latch that only springs open after destabilization of other regions. Our results provide new insights into the architecture and mechanism of the Tc toxin family.
Identifiants
pubmed: 31663026
doi: 10.1126/sciadv.aax6497
pii: aax6497
pmc: PMC6795518
doi:
Substances chimiques
Bacterial Proteins
0
Bacterial Toxins
0
Glycosides
0
Triterpenes
0
stichoposide
37341-37-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaax6497Subventions
Organisme : European Research Council
Pays : International
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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