ArticleProceedings of the National Academy of Sciences of the United States of America1992
Anthrax toxin protective antigen is activated by a cell surface protease with the sequence specificity and catalytic properties of furin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1992. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 papers.
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Who cites it
206 citing papers in PubMed, 459 citations in OpenAlex.
- Beyond Processing: Furin as a Central Hub in Viral Pathogenesis and Genetic Susceptibility.Biomolecules · 2025Review
- Protective antigen-mediated delivery of an anti-CRISPR protein for precision genome editing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- miR-24-3p Is Antiviral Against SARS-CoV-2 by Downregulating Critical Host Entry Factors.Viruses · 2024Article
- Metabolic Engineering of Glycofusion Bispecific Antibodies for α-Dystroglycanopathies.Antibodies (Basel, Switzerland) · 2024Article
- Alpha-1 antitrypsin inhibits Clostridium botulinum C2 toxin, Corynebacterium diphtheriae diphtheria toxin and B. anthracis fusion toxin.Scientific reports · 2024Article
- Early Circulating Edema Factor in Inhalational Anthrax Infection: Does It Matter?Microorganisms · 2024Article
- Comprehensive characterization of toxins during progression of inhalation anthrax in a non-human primate model.PLoS pathogens · 2022Article
- Monoclonal Antibodies for Bacterial Pathogens: Mechanisms of Action and Engineering Approaches for Enhanced Effector Functions.Biomedicines · 2022Review
- The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2.International journal of molecular sciences · 2022Review
- A Feasible Alternative Strategy Targeting Furin Disrupts SARS-CoV-2 Infection Cycle.Microbiology spectrum · 2022Article
- Article
- Using a Syrian (Golden) Hamster Biological Model for the Evaluation of Recombinant Anthrax Vaccines.Life (Basel, Switzerland) · 2021Article
- IgG-Engineered Protective Antigen for Cytosolic Delivery of Proteins into Cancer Cells.ACS central science · 2021Article
- Two approaches for the stabilization ofHuman vaccines & immunotherapeutics · 2021Article
- The Amino Acid at Position 8 of the Proteolytic Cleavage Site of the Mumps Virus Fusion Protein Affects Viral Proteolysis and Fusogenicity.Journal of virology · 2020Article
- Inhibitory Effects of a Reengineered Anthrax Toxin on Canine and Human Osteosarcoma Cells.Toxins · 2020Article
- Cryo-EM structure of the fully-loaded asymmetric anthrax lethal toxin in its heptameric pre-pore state.PLoS pathogens · 2020Article
- Article
- Targeting Cancer Gene Dependencies with Anthrax-Mediated Delivery of Peptide Nucleic Acids.ACS chemical biology · 2020Article
- Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming.Molecules (Basel, Switzerland) · 2020Article
146 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Proteolytic cleavage of the protective antigen (PA) protein of anthrax toxin at residues 164-167 is necessary for toxic activity. Cleavage by a cellular protease at this sequence, Arg-Lys-Lys-Arg, normally follows binding of PA to a cell surface receptor. We attempted to identify this protease by determining its sequence specificity and catalytic properties. Semi-random cassette mutagenesis was used to generate mutants with replacements of residues 164-167 by Arg, Lys, Ser, or Asn. Analysis of 19 mutant proteins suggested that lethal factor-dependent toxicity required the sequence Arg-Xaa-Xaa-Arg. Based on these data, three additional mutants were constructed with the sequences Ala-Lys-Lys-Arg, Arg-Lys-Lys-Ala, and Arg-Ala-Ala-Arg. Of these mutant proteins, Arg-Ala-Ala-Arg was toxic, confirming that the cellular protease can recognize the sequence Arg-Xaa-Xaa-Arg. The mutant containing the sequence Ala-Lys-Lys-Arg was also toxic but required > 13 times more protein to produce equivalent toxicity. This sequence specificity is similar to that of the ubiquitous subtilisin-like protease furin, which is involved in processing of precursors of certain receptors and growth factors. Therefore we tested whether a recombinant soluble furin would cleave PA. This furin derivative efficiently cleaved native PA and the Arg-Ala-Ala-Arg mutant but not the nontoxic PA mutants. In addition, previously identified inhibitors of furin blocked cleavage of receptor-bound PA. These data imply that furin is the cellular protease that activates PA, and that nearly all cell types contain at least a small amount of furin exposed on their cell surface.
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