期刊
SCIENCE ADVANCES
卷 5, 期 6, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aax2650
关键词
-
资金
- NSF
- [NIH-NHLBI R01-HL080050]
- [NIH-NIGMS GM117263-01A1]
Dinoflagelates and cyanobacteria produce saxitoxin (STX), a lethal bis-guanidinium neurotoxin causing paralytic shellfish poisoning. A number of metazoans have soluble STX-binding proteins that may prevent STX intoxication. However, their STX molecular recognition mechanisms remain unknown. Here, we present structures of saxiphilin (Sxph), a bullfrog high-affinity STX-binding protein, alone and bound to STX. The structures reveal a novel high-affinity STX-binding site built from a proto-pocket on a transferrin scaffold that also bears thyroglobulin domain protease inhibitor repeats. Comparison of Sxph and voltage-gated sodium channel STX-binding sites reveals a convergent toxin recognition strategy comprising a largely rigid binding site where acidic side chains and a cation-pi interaction engage STX. These studies reveal molecular rules for STX recognition, outline how a toxin-binding site can be built on a naive scaffold, and open a path to developing protein sensors for environmental STX monitoring and new biologics for STX intoxication mitigation.
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