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Cited by 9Escherichia coli research studiesToxin Mechanisms and ImmunotoxinsBacterial Genetics and Biotechnology

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Unconventional structure and mechanisms for membrane interaction and translocation of the NF-κB-targeting toxin AIP56

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Lisboa, Johnny, Pereira, Cassilda, Pinto, Rute D., Rodrigues, Inês S., Pereira, Liliana M. G., Pinheiro, Bruno, Oliveira, Pedro, Pereira, Pedro José Barbosa, Azevedo, Jorge E., Durand, Dominique, Benz, Roland, do Vale, Ana, dos Santos, Nuno M. S.·2023·Nature Communications
DOI 10.1038/s41467-023-43054-zPMC PMC10654918

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Abstract

Bacterial AB toxins are secreted key virulence factors that are internalized by target cells through receptor-mediated endocytosis, translocating their enzymatic domain to the cytosol from endosomes (short-trip) or the endoplasmic reticulum (long-trip). To accomplish this, bacterial AB toxins evolved a multidomain structure organized into either a single polypeptide chain or non-covalently associated polypeptide chains. The prototypical short-trip single-chain toxin is characterized by a receptor-binding domain that confers cellular specificity and a translocation domain responsible for pore formation whereby the catalytic domain translocates to the cytosol in an endosomal acidification-dependent way. In this work, the determination of the three-dimensional structure of AIP56 shows that, instead of a two-domain organization suggested by previous studies, AIP56 has three-domains: a non-LEE encoded effector C (NleC)-like catalytic domain associated with a small middle domain that contains the linker-peptide, followed by the receptor-binding domain. In contrast to prototypical single-chain AB toxins, AIP56 does not comprise a typical structurally complex translocation domain; instead, the elements involved in translocation are scattered across its domains. Thus, the catalytic domain contains a helical hairpin that serves as a molecular switch for triggering the conformational changes necessary for membrane insertion only upon endosomal acidification, whereas the middle and receptor-binding domains are required for pore formation.

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Metadata

Authors
Lisboa, J., Pereira, C., Pinto, R. D., Rodrigues, I. S., Pereira, L. M. G., Pinheiro, B., Oliveira, P., Pereira, P. J. B., Azevedo, J. E., Durand, D., Benz, R., do Vale, A., & dos Santos, N. M. S.
Affiliations
  • Universidade do Porto (PT)
  • Constructor University (DE)
Corresponding author
  • Lisboa, Johnny
  • dos Santos, Nuno M. S.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-11-16
Volume
14
Issue
1
Pages
7431-7431
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-43054-z
PMC
PMC10654918
OpenAlex
W4388722165
Cited by
9
References
2
Citations by year
2026: 1 · 2025: 4 · 2024: 4
FWCI
1.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by)
Funders
  • European Synchrotron Radiation Facility
  • Fundação para a Ciência e a Tecnologia (01-0145, COMPETE, POCI-01-0145, PO-CI-01-0145-FEDER-022122, PTDC/BIA-MIC/29910/2017, POCI-01-0145-FEDER-, COMPETE_2020, 2021.02251.CEECIND/CP1663/CT0016, POCI-01-, /2017, UIDB/04293/2020)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
  • Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
AB toxins, pore formation, endosomal acidification, receptor binding domain, catalytic domain, helical hairpin, endocytosis, virulence factors
MeSH terms
Bacterial Toxins, Endocytosis, Peptides, Endosomes, NF-kappa B, Protein Transport

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