ArticleThe Journal of biological chemistry2015
Exposure of neutralizing epitopes in the carboxyl-terminal domain of TcdB is altered by a proximal hypervariable region.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 26 citations in OpenAlex.
- The impact of TcdB conformational dynamics on vaccination against Clostridioides difficile.PLoS pathogens · 2026Article
- HumanbioRxiv : the preprint server for biology · 2025Article
- Mouse monoclonal antibodies againstInfection and immunity · 2025Article
- A sequence invariable region in TcdB2 is required for toxin escape fromJournal of bacteriology · 2024Article
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- CSPG4-dependent cytotoxicity formSphere · 2024Article
- Polyamines and hypusination are important forInfection and immunity · 2023Article
- Host Immunity and Immunization Strategies for Clostridioides difficile Infection.Clinical microbiology reviews · 2023Review
- Discovery of Hippo signaling as a regulator of CSPG4 expression and as a therapeutic target for Clostridioides difficile disease.PLoS pathogens · 2023Article
- Clostridioides difficile Toxin B Activates Group 3 Innate Lymphocytes.Infection and immunity · 2022Article
- Structural basis for CSPG4 as a receptor for TcdB and a therapeutic target in Clostridioides difficile infection.Nature communications · 2021Article
- Human C. difficile toxin-specific memory B cell repertoires encode poorly neutralizing antibodies.JCI insight · 2020Article
- Subtyping analysis reveals new variants and accelerated evolution of Clostridioides difficile toxin B.Communications biology · 2020Article
- Deletion of a 19-Amino-Acid Region in Clostridioides difficile TcdB2 Results in Spontaneous Autoprocessing and Reduced Cell Binding and Provides a Nontoxic Immunogen for Vaccination.Infection and immunity · 2019Article
- Structure of the full-length Clostridium difficile toxin B.Nature structural & molecular biology · 2019Article
- Toxin B Variants fromToxins · 2019Article
- Selection and characterization of ultrahigh potency designed ankyrin repeat protein inhibitors of C. difficile toxin B.PLoS biology · 2019Article
- Inhibition of bacterial toxin recognition of membrane components as an anti-virulence strategy.Journal of biological engineering · 2019Review
- Cell-penetrating peptides derived fromThe Journal of biological chemistry · 2018Article
- The Conserved Cys-2232 inFrontiers in microbiology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The sequence, activity, and antigenicity of TcdB varies between different strains of Clostridium difficile. As a result, ribotype-specific forms of TcdB exhibit different toxicities and are not strongly cross-neutralized. Using a combination of biochemical and immunological approaches, we compared two important variants of TcdB (TcdB012 and TcdB027) to identify the mechanisms through which sequence differences alter epitopes and activity of the toxin. These analyses led to the discovery of a critical variation in the 1753-1851 (B2') region of TcdB, which affects the exposure of neutralizing epitopes in the toxin. Sequence comparisons found that the B2' region exhibits only 77% identity and is the most variable sequence between the two forms of TcdB. A combination of biochemical, analytical, and mutagenesis experiments revealed that the B2' region promotes protein-protein interactions. These interactions appear to shield neutralizing epitopes that would otherwise be exposed in the toxin, an event found to be less prominent in TcdB012 due to sequence differences in the 1773-1780 and 1791-1798 regions of the B2' domain. When the carboxyl-terminal domains of TcdB012 and TcdB027 are swapped, neutralization experiments suggest that the amino terminus of TcdB interacts with the B2' region and impacts the exposure of neutralizing epitopes in the carboxyl terminus. Collectively, these data suggest that variations in the B2' region affect protein-protein interactions within TcdB and that these interactions influence the exposure of neutralizing epitopes.
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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.