ArticleThe Journal of biological chemistry2016
Anthrax Toxin Protective Antigen Variants That Selectively Utilize either the CMG2 or TEM8 Receptors for Cellular Uptake and Tumor Targeting.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Protective effect of anthrax toxin receptor 2 polymorphism rs4333130 against the risk of ankylosing spondylitis.Medicine · 2020Pooled it
- Review
- AB Toxins as High-Affinity Ligands for Cell Targeting in Cancer Therapy.International journal of molecular sciences · 2023Review
- ERK and c-Myc signaling in host-derived tumor endothelial cells is essential for solid tumor growth.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Receptor-enhanced immunogenicity of anthrax protective antigen is primarily mediated by capillary morphogenesis Protein-2.Vaccine · 2022Article
- Role of site-directed mutagenesis and adjuvants in the stability and potency of anthrax protective antigen.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Review
- Intein-mediated cytoplasmic reconstitution of a split toxin enables selective cell ablation in mixed populations and tumor xenografts.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Capillary morphogenesis gene 2 maintains gastric cancer stem-like cell phenotype by activating a Wnt/β-catenin pathway.Oncogene · 2018Article
- CMG2 Expression Is an Independent Prognostic Factor for Soft Tissue Sarcoma Patients.International journal of molecular sciences · 2017Article
- Tumor Targeting and Drug Delivery by Anthrax Toxin.Toxins · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The protective antigen (PA) moiety of anthrax toxin binds to cellular receptors and mediates the translocation of the two enzymatic moieties of the toxin to the cytosol. Two PA receptors are known, with capillary morphogenesis protein 2 (CMG2) being the more important for pathogenesis and tumor endothelial marker 8 (TEM8) playing a minor role. The C-terminal PA domain 4 (PAD4) has extensive interactions with the receptors and is required for binding. Our previous study identified PAD4 variants having enhanced TEM8 binding specificity. To obtain PA variants that selectively bind to CMG2, here we performed phage display selections using magnetic beads having bound CMG2. We found that PA residue isoleucine 656 plays a critical role in PA binding to TEM8 but has a much lesser effect on PA binding to CMG2. We further characterized the role of residue 656 in distinguishing PA binding to CMG2 versus TEM8 by substituting it with the other 19 amino acids. Of the resulting variants, PA I656Q and PA I656V had significantly reduced activity on TEM8-expressing CHO cells but maintained their activity on CMG2-expressing CHO cells. The preference of these PA mutants for CMG2 over TEM8 was further demonstrated using mouse embryonic fibroblast cells and mice deficient in the CMG2 and/or the TEM8 receptors. The structural basis of the alterations in the receptor binding activities of these mutants is also discussed.
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Registered trials
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