Journal Article

Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins

Nixon, Samantha A., Provasi, Davide, Hajare, Holly S., Leighfield, Tod A., Arlinghaus, Kandis M., Du Bois, J., Park, Elizabeth R., Neu, Eduard, Konovalov, Kirill, Filizola, Marta, Minor, Daniel L., Mulcahy, John V., Chen, Zhou, Zakrzewska, Sandra

2025

Overview

Dinoflagellates and cyanobacteria produce saxitoxin (STX) and ~50 congeners that disrupt bioelectrical signals by blocking voltage-gated sodium channels (Na V s). Consuming seafood carrying these toxins causes paralytic shellfish poisoning (PSP). Although Na V s and anuran STX binding proteins (saxiphilins, Sxphs) use convergent STX binding modes, the structural basis for STX congener recognition is unknown. Here, we show that American bullfrog ( Rana catesbeiana ) Rc Sxph and High Himalaya frog ( Nanorana parkeri ) Np Sxph sequester STX congeners using a ‘lock and key’ mode shared with STX. Importantly, functional studies demonstrate that Sxph ‘toxin sponges’ reverse Na V block by multiple STX congeners and detect these toxins in a radioligand binding assay (RBA) used for environmental testing. Together, our study establishes how Sxphs sequester select neurotoxins and uncover STX congener-specific interactions distinct from Na V s. These findings expand understanding of toxin sponge action and provide a foundation for strategies to monitor and mitigate the harmful effects of STX congeners. Dinoflagellates and cyanobacteria produce saxitoxin (STX) congeners that block voltage-gated sodium channels. Here authors show how amphibians may sequester STX congeners using a ‘lock and key’ mode, expanding the understanding of toxic sponge action.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/114/2410 / 631/45/269 / 631/535/1266 / 631/57/2270/1140 / 82/80 / 82/83 / 9/74 / Amphibians / Animals / Anura - metabolism / Binding / Bioelectricity / Blocking / Carrier Proteins - chemistry / Carrier Proteins - metabolism / Channel gating / Channels / Congeners / Cyanobacteria / Dinoflagellates / Dinoflagellida - metabolism / Environmental testing / Humanities and Social Sciences / Microorganisms / multidisciplinary / Neurotoxins / Neutralization / Paralytic shellfish poisoning / Protein Binding / Rana catesbeiana - metabolism / Saxitoxin / Saxitoxin - chemistry / Saxitoxin - metabolism / Saxitoxin - toxicity / Science / Science (multidisciplinary) / Seafood / Shellfish / Sodium / Sodium channels (voltage-gated) / Toxins / Voltage-Gated Sodium Channels - metabolism