8v67
Nanorana parkeri saxiphilin:C1 (co-crystal)
Structural highlights
FunctionPublication Abstract from PubMedDinoflagellates 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) 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 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. Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins.,Zakrzewska S, Nixon SA, Chen Z, Hajare HS, Park ER, Mulcahy JV, Arlinghaus KM, Neu E, Konovalov K, Provasi D, Leighfield TA, Filizola M, Du Bois J, Minor DL Jr Nat Commun. 2025 Apr 24;16(1):3885. doi: 10.1038/s41467-025-58903-2. PMID:40274765[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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