ArticleJournal of molecular biology2012
Domain flexibility modulates the heterogeneous assembly mechanism of anthrax toxin protective antigen.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Dynamic S-acylation controls CMG2 maturation extracellular matrix regulation and anthrax toxin susceptibility in vivo.Nature communications · 2026Article
- Recombinant full-lengthFrontiers in immunology · 2022Article
- Solution Structures ofToxins · 2021Article
- Different mechanisms of two anti-anthrax protective antigen antibodies and function comparison between them.BMC infectious diseases · 2019Article
- Accurate and selective quantification of anthrax protective antigen in plasma by immunocapture and isotope dilution mass spectrometry.The Analyst · 2019Article
- The Ins and Outs of Anthrax Toxin.Toxins · 2016Review
- Characterization of Protein-Protein Interfaces through a Protein Contact Network Approach.Frontiers in bioengineering and biotechnology · 2015Article
- Long-range stabilization of anthrax protective antigen upon binding to CMG2.Biochemistry · 2014Article
- Review
- Engineering anthrax toxin variants that exclusively form octamers and their application to targeting tumors.The Journal of biological chemistry · 2013Article
- Electrostatic ratchet in the protective antigen channel promotes anthrax toxin translocation.The Journal of biological chemistry · 2012Article
- Obstructing toxin pathways by targeted pore blockage.Chemical reviews · 2012Review
- Anthrax toxin protective antigen integrates poly-γ-D-glutamate and pH signals to sense the optimal environment for channel formation.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Small molecule inhibitors of Bacillus anthracis protective antigen proteolytic activation and oligomerization.Journal of medicinal chemistry · 2012Article
- Bacillus anthracis edema factor substrate specificity: evidence for new modes of action.Toxins · 2012Review
- Ratcheting up protein translocation with anthrax toxin.Protein science : a publication of the Protein Society · 2012Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The three protein components of anthrax toxin are nontoxic individually, but they form active holotoxin complexes upon assembly. The role of the protective antigen (PA) component of the toxin is to deliver two other enzyme components, lethal factor and edema factor, across the plasma membrane and into the cytoplasm of target cells. PA is produced as a proprotein, which must be proteolytically activated; generally, cell surface activation is mediated by a furin family protease. Activated PA can then assemble into one of two noninterconverting oligomers, a homoheptamer and a homooctamer, which have unique properties. Herein we describe molecular determinants that influence the stoichiometry of PA in toxin complexes. By tethering PA domain 4 (D4) to domain 2 with two different-length cross-links, we can control the relative proportions of PA heptamers and octamers. The longer cross-link favors octamer formation, whereas the shorter one favors formation of the heptamer. X-ray crystal structures of PA (up to 1.45 Å resolution), including these cross-linked PA constructs, reveal that a hinge-like movement of D4 correlates with the relative preference for each oligomeric architecture. Furthermore, we report the conformation of the flexible loop containing the furin cleavage site and show that, for efficient processing, the furin site cannot be moved ~5 or 6 residues within the loop. We propose that there are different orientations of D4 relative to the main body of PA that favor the formation of either the heptamer or the octamer.
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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.