ArticleScience advances2019
Structure of the saxiphilin:saxitoxin (STX) complex reveals a convergent molecular recognition strategy for paralytic toxins.
Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Batrachotoxin-sensitive sodium channels in toxic birds challenge "target mutation" strategy of toxin autoresistance.iScience · 2026Article
- Saxiphilin is a broad-spectrum toxin sponge for C13-modified saxitoxins.Structure (London, England : 1993) · 2026Article
- Saxiphilin functions as a toxin sponge protein that counteracts the effects of saxitoxin poisoning.Nature communications · 2026Article
- The Venom Revolution in Biomedicine: Unlocking Nature's Toxin Toolkit for Therapeutic Innovation.Toxicology reports · 2026Review
- Development of an Automated Cell-Based Assay for the Detection of the Functional Activity of Saxitoxin.Toxins · 2026Article
- Saxiphilin is a broad-spectrum toxin sponge for C13-modified saxitoxins.bioRxiv : the preprint server for biology · 2026Article
- Saxiphilin functions as a 'toxin sponge' protein that counteracts the effects of saxitoxin poisoning.bioRxiv : the preprint server for biology · 2025Article
- Saxitoxin: A Comprehensive Review of Its History, Structure, Toxicology, Biosynthesis, Detection, and Preventive Implications.Marine drugs · 2025Review
- Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins.Nature communications · 2025Article
- An Unusual Two-Domain Thyropin from Tick Saliva: NMR Solution Structure and Highly Selective Inhibition of Cysteine Cathepsins Modulated by Glycosaminoglycans.International journal of molecular sciences · 2024Article
- Tuning phenylalanine fluorination to assess aromatic contributions to protein function and stability in cells.Nature communications · 2023Article
- Definition of a saxitoxin (STX) binding code enables discovery and characterization of the anuran saxiphilin family.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Convergent evolution of toxin resistance in animals.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Comparative analysis defines a broader FMRFamide-gated sodium channel family and determinants of neuropeptide sensitivity.The Journal of biological chemistry · 2022Article
- Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on "toxin sponge" proteins.The Journal of general physiology · 2021Article
- Cation-π Interactions and their Functional Roles in Membrane Proteins.Journal of molecular biology · 2021Review
- Rapid toxin sequestration modifies poison frog physiology.The Journal of experimental biology · 2021Article
- Mechanisms Applied by Protein Inhibitors to Inhibit Cysteine Proteases.International journal of molecular sciences · 2021Review
- Host-Parasite Interaction of Atlantic salmon (Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Dinoflagelates and cyanobacteria produce saxitoxin (STX), a lethal bis-guanidinium neurotoxin causing paralytic shellfish poisoning. A number of metazoans have soluble STX-binding proteins that may prevent STX intoxication. However, their STX molecular recognition mechanisms remain unknown. Here, we present structures of saxiphilin (Sxph), a bullfrog high-affinity STX-binding protein, alone and bound to STX. The structures reveal a novel high-affinity STX-binding site built from a "proto-pocket" on a transferrin scaffold that also bears thyroglobulin domain protease inhibitor repeats. Comparison of Sxph and voltage-gated sodium channel STX-binding sites reveals a convergent toxin recognition strategy comprising a largely rigid binding site where acidic side chains and a cation-π interaction engage STX. These studies reveal molecular rules for STX recognition, outline how a toxin-binding site can be built on a naïve scaffold, and open a path to developing protein sensors for environmental STX monitoring and new biologics for STX intoxication mitigation.
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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.