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Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins

Author

Listed:
  • Sandra Zakrzewska

    (University of California)

  • Samantha A. Nixon

    (University of California)

  • Zhou Chen

    (University of California
    Shanghai Jiao Tong University School of Medicine)

  • Holly S. Hajare

    (Stanford University)

  • Elizabeth R. Park

    (Stanford University)

  • John V. Mulcahy

    (Stanford University)

  • Kandis M. Arlinghaus

    (National Centers for Coastal Ocean Science)

  • Eduard Neu

    (Ichan School of Medicine at Mount Sinai)

  • Kirill Konovalov

    (Ichan School of Medicine at Mount Sinai)

  • Davide Provasi

    (Ichan School of Medicine at Mount Sinai)

  • Tod A. Leighfield

    (National Centers for Coastal Ocean Science)

  • Marta Filizola

    (Ichan School of Medicine at Mount Sinai)

  • J. Bois

    (Stanford University)

  • Daniel L. Minor

    (University of California
    University of California
    University of California
    University of California)

Abstract

Dinoflagellates and cyanobacteria produce saxitoxin (STX) and ~50 congeners that disrupt bioelectrical signals by blocking voltage-gated sodium channels (NaVs). Consuming seafood carrying these toxins causes paralytic shellfish poisoning (PSP). Although NaVs 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) RcSxph and High Himalaya frog (Nanorana parkeri) NpSxph sequester STX congeners using a ‘lock and key’ mode shared with STX. Importantly, functional studies demonstrate that Sxph ‘toxin sponges’ reverse NaV 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 NaVs. These findings expand understanding of toxin sponge action and provide a foundation for strategies to monitor and mitigate the harmful effects of STX congeners.

Suggested Citation

  • Sandra Zakrzewska & Samantha A. Nixon & Zhou Chen & Holly S. Hajare & Elizabeth R. Park & John V. Mulcahy & Kandis M. Arlinghaus & Eduard Neu & Kirill Konovalov & Davide Provasi & Tod A. Leighfield & , 2025. "Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58903-2
    DOI: 10.1038/s41467-025-58903-2
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    References listed on IDEAS

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    1. Yanhui Dai & Shangbo Yang & Dan Zhao & Chuanmin Hu & Wang Xu & Donald M. Anderson & Yun Li & Xiao-Peng Song & Daniel G. Boyce & Luke Gibson & Chunmiao Zheng & Lian Feng, 2023. "Coastal phytoplankton blooms expand and intensify in the 21st century," Nature, Nature, vol. 615(7951), pages 280-284, March.
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