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Zheng Liu, Conceptualization, Investigation, Visualization, Writing - original draft,1 Sicai Zhang, Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing,2 Peng Chen, Conceptualization, Methodology,1 Songhai Tian, Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing,2 Ji Zeng, Investigation, Resources,2 Kay Perry, Investigation,3 Min Dong, Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Visualization, Writing - original draft, Writing - review & editing,2 and Rongsheng Jin, Conceptualization, Data curation, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing1

34. Chen P., Lam K. H., Liu Z., Mindlin F. A., Chen B., Gutierrez C. B., Huang L., Zhang Y., Hamza T., Feng H., Matsui T., Bowen M. E., Perry K., Jin R.,

Citation:Lee K, Gu S, Jin L, Le TTN, Cheng LW, Strotmeier J, et al. (2013) Structure of a Bimodular Botulinum Neurotoxin Complex Provides Insights into Its Oral Toxicity. PLoS Pathog 9(10):

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We thank Robbin Newlin for assistance with tissue preparation and immunostaining. We thank Core H of the Consortium for Functional Glycomics (CFG) for glycan array screening. This work was partly supported by National Institute of Allergy and Infectious Diseases (NIAID) grant R01AI091823 to Rongsheng Jin.

16.Gu, S.; Rumpel, S.; Zhou, J.; Strotmeier, J.; Bigalke, H.; Perry, K.; Shoemaker, C.B.; Rummel, A.; Jin, R. Botulinum neurotoxin is shielded by NTNHA in an interlocked complex. Science 2012, 335, 977-981.

17.Lee, K.; Gu, S.; Jin, L.; Le, T.T.; Cheng, L.W.; Strotmeier, J.; Kruel, A.M.; Yao, G.; Perry, K.; et al. Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity. PLoSPathog. 2013, 9, e1003690.

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22.Fujinaga, Y.; Inoue, K.; Watanabe, S.; Yokota, K.; Hirai, Y.; Nagamachi, E.; Oguma, K. The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine, leading to the efficient absorption of the toxin. Microbiology 1997, 143, 3841-3847.

23.Nishikawa, A.; Uotsu, N.; Arimitsu, H.; Lee, J.C.; Miura, Y.; Fujinaga, Y.; Nakada, H.; Watanabe, T.; Ohyama, T.; Sakano, Y.; et al. The receptor and transporter for internalization of Clostridium botulinum type C progenitor toxin into HT-29 cells. Biochem. Biophys. Res. Commun. 2004, 319, 327-333.

22. Chen B, Liu Z, Perry K, Jin R. Structure of the glucosyltransferase domain of tcda in complex with rhoa provides insights into substrate recognition. Sci Rep (2022) 12(1):9028. doi: 10.1038/s41598-022-12909-8

32. Kroh HK, Chandrasekaran R, Rosenthal K, Woods R, Jin X, Ohi MD, et al. Use of a neutralizing antibody helps identify structural features critical for binding of clostridium difficile toxin tcda to the host cell surface. J Biol Chem (2017) 292(35):14401–12. doi: 10.1074/jbc.M117.781112

49. Chen P, Jin R. Receptor binding mechanisms of clostridioides difficile toxin b and implications for therapeutics development. FEBS J (2021). doi: 10.1111/febs.16310

51. Kroh HK, Chandrasekaran R, Zhang Z, Rosenthal K, Woods R, Jin X, et al. A neutralizing antibody that blocks delivery of the enzymatic cargo of clostridium difficile toxin tcdb into host cells. J Biol Chem (2018) 293(3):941–52. doi: 10.1074/jbc.M117.813428

59. Lam K-H, Perry K, Shoemaker CB, Jin R. Two vhh antibodies neutralize botulinum neurotoxin E1 by blocking its membrane translocation in host cells. Toxins (Basel) (2020) 12(10):616. doi: 10.3390/toxins12100616