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Structure of the saxiphilin:saxitoxin (STX) complex reveals a convergent molecular recognition strategy for paralytic toxins.
- Source :
-
Science advances [Sci Adv] 2019 Jun 19; Vol. 5 (6), pp. eaax2650. Date of Electronic Publication: 2019 Jun 19 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Amino Acid Sequence
Animals
Binding Sites drug effects
Binding Sites physiology
Cell Line
Cyanobacteria metabolism
Humans
Peptide Hydrolases metabolism
Protease Inhibitors pharmacology
Protein Binding drug effects
Protein Binding physiology
Rana catesbeiana
Sf9 Cells
Sodium Channels metabolism
Thyroglobulin metabolism
Transferrin metabolism
Carrier Proteins metabolism
Saxitoxin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2375-2548
- Volume :
- 5
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Science advances
- Publication Type :
- Academic Journal
- Accession number :
- 31223657
- Full Text :
- https://doi.org/10.1126/sciadv.aax2650