8.B.47.  The Saxitoxin (STX) Family 

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. Zakrzewska et al. 2025 showed 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 an understanding of toxin sponge action and provide a foundation for strategies to monitor and mitigate the harmful effects of STX congeners (Zakrzewska et al. 2025).


 

References:

Zakrzewska, S., S.A. Nixon, Z. Chen, H.S. Hajare, E.R. Park, J.V. Mulcahy, K.M. Arlinghaus, E. Neu, K. Konovalov, D. Provasi, T.A. Leighfield, M. Filizola, J. Du Bois, and D.L. Minor, Jr. (2025). Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins. Nat Commun 16: 3885.
Examples:

TC#NameOrganismal TypeExample
8.B.47.1.1

Saxitoxin (STX) of 391 aas and 1 N-terminal TMSs. The active toxin is 41 aas long. See family description for more details (Zakrzewska et al. 2025).  

STX of Takifugu pardalis (Panther puffer) (Tetraodon pardalis)