ArticleThe Journal of biological chemistry2010
Effects of introducing a single charged residue into the phenylalanine clamp of multimeric anthrax protective antigen.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
14 citing papers in PubMed, 24 citations in OpenAlex.
- Asymmetric Cryo-EM Structure of Anthrax Toxin Protective Antigen Pore with Lethal Factor N-Terminal Domain.Toxins · 2017Article
- Article
- Article
- Polylysine-mediated translocation of the diphtheria toxin catalytic domain through the anthrax protective antigen pore.Biochemistry · 2014Article
- Designing inhibitors of anthrax toxin.Expert opinion on drug discovery · 2014Review
- Anthrax toxin-induced rupture of artificial lipid bilayer membranes.The Journal of chemical physics · 2013Article
- Obstructing toxin pathways by targeted pore blockage.Chemical reviews · 2012Review
- Interactions of high-affinity cationic blockers with the translocation pores of B. anthracis, C. botulinum, and C. perfringens binary toxins.Biophysical journal · 2012Article
- Ratcheting up protein translocation with anthrax toxin.Protein science : a publication of the Protein Society · 2012Review
- Ultrasensitive detection of protein translocated through toxin pores in droplet-interface bilayers.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Cys-Cys cross-linking shows contact between the N-terminus of lethal factor and Phe427 of the anthrax toxin pore.Biochemistry · 2011Article
- The unfolding story of anthrax toxin translocation.Molecular microbiology · 2011Review
- Interactions of anthrax lethal factor with protective antigen defined by site-directed spin labeling.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Multimeric pores formed in the endosomal membrane by the Protective Antigen moiety of anthrax toxin translocate the enzymatic moieties of the toxin to the cytosolic compartment of mammalian cells. There is evidence that the side chains of the Phe(427) residues come into close proximity with one another in the lumen of the pore and form a structure, termed the Phe clamp, that catalyzes the translocation process. In this report we describe the effects of replacing Phe(427) in a single subunit of the predominantly heptameric pore with a basic or an acidic amino acid. Incorporating any charged residue at this position inhibited cytotoxicity >or=1,000-fold in our standard assay and caused strong inhibition of translocation in a planar phospholipid bilayer system. His and Glu were the most strongly inhibitory residues, ablating both cytotoxicity and translocation. Basic residues at position 427 prevented the Phe clamp from interacting with a translocation substrate to form a seal against the passage of ions and accelerated dissociation of the substrate from the pore. Acidic residues, in contrast, allowed the seal to form and the substrate to remain firmly bound, but blocked its passage, perhaps via electrostatic interactions with the positively charged N-terminal segment. Our findings are discussed in relation to the role of the Phe clamp in a Brownian ratchet model of translocation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.