Structure of the saxiphilin:saxitoxin (STX) complex reveals a convergent molecular recognition strategy for paralytic toxins

Yen, Tien-Jui; Lolicato, Marco; Thomas-Tran, Rhiannon; Du Bois, J.; Minor, Daniel L.

doi:10.1126/sciadv.aax2650

Title: Structure of the saxiphilin:saxitoxin (STX) complex reveals a convergent molecular recognition strategy for paralytic toxins

Journal Article · Wed Jun 19 00:00:00 EDT 2019 · Science Advances

DOI:https://doi.org/10.1126/sciadv.aax2650· OSTI ID:1599801

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Univ. of California, San Francisco, CA (United States)
Univ. of California, San Francisco, CA (United States); Gilead Sciences, Foster City, CA (United States)
Univ. of California, San Francisco, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

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-π interaction engage STX. These studies reveal molecular rules for STX recognition, outline how a toxin-binding site can be built on a naïve scaffold, and open a path to developing protein sensors for environmental STX monitoring and new biologics for STX intoxication mitigation.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); National Science Foundation (NSF)

Grant/Contract Number:: AC02-05CH11231; NIH-NHLBI R01-H6080050; NIH-NIGMS GM117263-01A1

OSTI ID:: 1599801

Journal Information:: Science Advances, Vol. 5, Issue 6; ISSN 2375-2548

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 13 works

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