Crystal structures of OrfX1, OrfX2 and the OrfX1-OrfX3 complex from the orfX gene cluster of botulinum neurotoxin E1.

OrfX1 OrfX2 OrfX3 bacterial toxin botulinum neurotoxin orfX gene cluster

Journal

FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157

Informations de publication

Date de publication:
02 2023
Historique:
received: 07 12 2022
accepted: 12 12 2022
pmc-release: 01 02 2024
pubmed: 19 1 2023
medline: 3 3 2023
entrez: 18 1 2023
Statut: ppublish

Résumé

Botulinum neurotoxins (BoNTs) are among the most lethal toxins known to humans, comprising seven established serotypes termed BoNT/A-G encoded in two types of gene clusters (ha and orfX) in BoNT-producing clostridia. The ha cluster encodes four non-toxic neurotoxin-associated proteins (NAPs) that assemble with BoNTs to protect and enhance their oral toxicity. However, the structure and function of the orfX-type NAPs remain largely unknown. Here, we report the crystal structures for OrfX1, OrfX2, and an OrfX1-OrfX3 complex, which are encoded in the orfX cluster of a BoNT/E1-producing Clostridium botulinum strain associated with human foodborne botulism. These structures lay the foundation for future studies on the potential roles of OrfX proteins in oral intoxication and pathogenesis of BoNTs.

Identifiants

pubmed: 36653893
doi: 10.1002/1873-3468.14576
pmc: PMC10019085
mid: NIHMS1877916
doi:

Substances chimiques

Botulinum Toxins, Type A EC 3.4.24.69

Banques de données

RefSeq
['ACSC01000002']

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

524-537

Subventions

Organisme : NIGMS NIH HHS
ID : P30 GM124165
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI091823
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI125704
Pays : United States
Organisme : NIH HHS
ID : S10 OD021527
Pays : United States

Informations de copyright

© 2023 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

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Auteurs

Linfeng Gao (L)

Department of Physiology and Biophysics, University of California, Irvine, CA, USA.

Kwok-Ho Lam (KH)

Department of Physiology and Biophysics, University of California, Irvine, CA, USA.

Shun Liu (S)

Department of Physiology and Biophysics, University of California, Irvine, CA, USA.

Adina Przykopanski (A)

Institute of Toxicology, Hannover Medical School, Germany.

Johanna Lübke (J)

Institute of Toxicology, Hannover Medical School, Germany.

Ruifeng Qi (R)

Department of Physiology and Biophysics, University of California, Irvine, CA, USA.

Maren Krüger (M)

Biological Toxins, Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.

Maria B Nowakowska (MB)

Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Finland.

Katja Selby (K)

Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Finland.

François P Douillard (FP)

Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Finland.

Martin B Dorner (MB)

Biological Toxins, Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.

Kay Perry (K)

NE-CAT and Department of Chemistry and Chemical Biology, Argonne National Laboratory, Cornell University, IL, Argonne, USA.

Miia Lindström (M)

Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Finland.

Brigitte G Dorner (BG)

Biological Toxins, Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.

Andreas Rummel (A)

Institute of Toxicology, Hannover Medical School, Germany.

Rongsheng Jin (R)

Department of Physiology and Biophysics, University of California, Irvine, CA, USA.

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Classifications MeSH