Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins

Journal Article · Wed Jan 01 00:00:00 EST 2025 · Nature Communications

DOI:https://doi.org/10.1038/s41467-025-58903-2· OSTI ID:2570836

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

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.

• Research Organization: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
• Sponsoring Organization: US Department of Energy; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23), Biological Systems Science Division (SC-23.2 )
• Grant/Contract Number: AC02-05CH11231
• OSTI ID: 2570836
• Journal Information: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 16
• Country of Publication: United States
• Language: English