ArticleCell2020
Recognition of Semaphorin Proteins by P. sordellii Lethal Toxin Reveals Principles of Receptor Specificity in Clostridial Toxins.
Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- From colonization to infection: Genomic evolution of Clostridioides difficile pathogenesis.Cell reports · 2026Review
- Dissecting conserved molecular mechanisms of biological toxin activity through CRISPR screening.Biochemical Society transactions · 2026Review
- Chronic Basal Ganglia Infarction With PCR-IdentifiedCase reports in pathology · 2026Article
- Applications of Genome-wide Screening of CRISPR/Cas9 Knockout Library in Identifying Novel Molecular Targets for Xenobiotics.Environment & health (Washington, D.C.) · 2025Review
- High-throughput discovery of transmembrane helix dimers from human single-pass membrane proteins with TOXGREEN sort-seq.PNAS nexus · 2025Article
- De novo design of potent inhibitors of clostridial family toxins.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Design, performance, processing, and validation of a pooled CRISPR perturbation screen for bacterial toxins.Nature protocols · 2025Review
- Bacterial exotoxins in medicine: potential value and perspectives.International journal of medical sciences · 2025Review
- Bacterial toxins induce non-canonical migracytosis to aggravate acute inflammation.Cell discovery · 2024Article
- Integrating genome-wide CRISPR screens and in silico drug profiling for targeted antidote development.Nature protocols · 2024Review
- Unlocking biological mechanisms with integrative functional genomics approaches.Molecules and cells · 2024Review
- Identification of a hemorrhagic determinant inMicrobiology spectrum · 2024Article
- Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution.Toxins · 2024Review
- Molecular basis of TMPRSS2 recognition by Paeniclostridium sordellii hemorrhagic toxin.Nature communications · 2024Article
- SEMA6B induces macrophage-mediated inflammation and hepatocyte apoptosis in hepatitis B virus-related acute-on-chronic liver failure.Theranostics · 2024Article
- An Updated View on the Cellular Uptake and Mode-of-Action of Clostridioides difficile Toxins.Advances in experimental medicine and biology · 2024Article
- Structural dynamics of the CROPs domain control stability and toxicity of Paeniclostridium sordellii lethal toxin.Nature communications · 2023Article
- SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability.Nature communications · 2023Article
- Gaining New Insights into Fundamental Biological Pathways by Bacterial Toxin-Based Genetic Screens.Bioengineering (Basel, Switzerland) · 2023Review
- Identification of indocyanine green as a STT3B inhibitor against mushroom α-amanitin cytotoxicity.Nature communications · 2023Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Pathogenic clostridial species secrete potent toxins that induce severe host tissue damage. Paeniclostridium sordellii lethal toxin (TcsL) causes an almost invariably lethal toxic shock syndrome associated with gynecological infections. TcsL is 87% similar to C. difficile TcdB, which enters host cells via Frizzled receptors in colon epithelium. However, P. sordellii infections target vascular endothelium, suggesting that TcsL exploits another receptor. Here, using CRISPR/Cas9 screening, we establish semaphorins SEMA6A and SEMA6B as TcsL receptors. We demonstrate that recombinant SEMA6A can protect mice from TcsL-induced edema. A 3.3 Å cryo-EM structure shows that TcsL binds SEMA6A with the same region that in TcdB binds structurally unrelated Frizzled. Remarkably, 15 mutations in this evolutionarily divergent surface are sufficient to switch binding specificity of TcsL to that of TcdB. Our findings establish semaphorins as physiologically relevant receptors for TcsL and reveal the molecular basis for the difference in tissue targeting and disease pathogenesis between highly related toxins.
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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.