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ARS Home » Pacific West Area » Albany, California » Western Regional Research Center » Foodborne Toxin Detection and Prevention Research » Research » Publications at this Location » Publication #289283

Title: Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity

Author
item LEE, KWANGKOOK - Sanford And Burnham Medical Research Institute
item GU, SHENGYAN - Sanford And Burnham Medical Research Institute
item JIN, LEI - Sanford And Burnham Medical Research Institute
item LE, THI TUC NGHI - Hannover University
item Cheng, Luisa
item STROTMEIER, JASMIN - Hannover University
item KRUE, ANNA - Hannover University
item PERRY, KAY - Cornell University
item YAO, GUORUI - Sanford And Burnham Medical Research Institute
item RUMMEL, ANDREAS - Sanford And Burnham Medical Research Institute
item JIN, RONGSHENG - Sanford And Burnham Medical Research Institute

Submitted to: PLoS Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/11/2013
Publication Date: 10/10/2013
Citation: Lee, K., Gu, S., Jin, L., Le, T., Cheng, L.W., Strotmeier, J., Krue, A.M., Perry, K., Yao, G., Rummel, A., Jin, R. 2013. Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity. PLoS Pathogens. 9(10):e1003690. DOI: 10.1371/journal.ppat.1003690.

Interpretive Summary: In this study, scientists resolved the structure of the large botulinum neurotoxin complex. The structure revealed toxin domains important in protection from degradation in the harsh environment of the intestinal tract and in intestinal absorption. Researchers also identified sugar inhibitors of toxin-intestinal binding, showing a new way to counteract toxin ingestion.

Technical Abstract: Botulinum neurotoxins (BoNTs) are highly potent oral poisons produced by Clostridium botulinum. BoNTs are secreted along with several auxiliary proteins forming progenitor toxin complexes (PTC). Here, we report the structure of a ~760 kDa 14-subunit PTC using a combination of X-ray crystallography and electron microscopy. Structural and functional studies showed that the PTC consists of two relatively independent sub-complexes that are responsible for BoNT protection and absorption in the harsh environment of the gastrointestinal tract. Moreover, efficient BoNT intestinal absorption is mediated by the PTC’s nine glycan-binding sites through multivalent interactions with host carbohydrate receptors lining the intestine. Importantly, we identified an inhibitory monosaccharide that blocked oral BoNT intoxication in mice, thus suggesting that receptor mimicry approaches could be used as novel countermeasures for BoNTs.