Structure of a Bimodular Botulinum Neurotoxin Complex Provides Insights into Its Oral Toxicity

PLoS Pathogens

Volumn 9, Issue 10, 2013, Pages

  Lee, Kwangkook ^a   Gu, Shenyan ^a   Jin, Lei ^b   Le, Thi Tuc Nghi ^c   Cheng, Luisa W ^d   Strotmeier, Jasmin ^c   Kruel, Anna Magdalena ^c   Yao, Guorui ^a   Perry, Kay ^e   Rummel, Andreas ^c   Jin, Rongsheng ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b BURNHAM INSTITUTE   (United States)

^c HANNOVER MEDICAL SCHOOL   (Germany)

^d WESTERN REGIONAL RESEARCH CENTER   (United States)

^e Department of Obstetrics Gynecology   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BOTULINUM TOXIN; CARBOHYDRATE RECEPTOR; HEMAGGLUTININ; HEMAGGLUTININ 17; ISOPROPYL THIOGALACTOSIDE; PEPSIN A; RECEPTOR; TRYPSIN; UNCLASSIFIED DRUG;

ABSORPTION; ARTICLE; BOTULISM; CELL STRAIN CACO 2; CRYSTAL STRUCTURE; CRYSTALLIZATION; ELECTRON MICROSCOPY; FEMALE; FLUORESCENCE; GASTROINTESTINAL TRACT; INTESTINE EPITHELIUM; ISOTHERMAL TITRATION CALORIMETRY; MOLECULAR DOCKING; MOUSE; MOUTH TOXICITY; NONHUMAN; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PROTEIN PURIFICATION; PROTEIN STRUCTURE; TOXICITY; ULTRACENTRIFUGATION; X RAY CRYSTALLOGRAPHY;

ANIMALS; BOTULINUM TOXINS; BOTULISM; CLOSTRIDIUM BOTULINUM; FEMALE; MICE; MULTIPROTEIN COMPLEXES; PROTEIN STRUCTURE, QUATERNARY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84887286760     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003690     Document Type: Article

References (64)

1. Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, et al. (2001) Botulinum toxin as a biological weapon: medical and public health management. JAMA 285: 1059-1070.
2. Bigalke H, (2013) Botulinum toxin: application, safety, and limitations. Curr Top Microbiol Immunol 364: 307-317.
3. Collins MD, East AK, (1998) Phylogeny and taxonomy of the food-borne pathogen Clostridium botulinum and its neurotoxins. J Appl Microbiol 84: 5-17.
4. Cheng LW, Onisko B, Johnson EA, Reader JR, Griffey SM, et al. (2008) Effects of purification on the bioavailability of botulinum neurotoxin type A. Toxicology 249: 123-129.
5. Gu S, Rumpel S, Zhou J, Strotmeier J, Bigalke H, et al. (2012) Botulinum neurotoxin is shielded by NTNHA in an interlocked complex. Science 335: 977-981.
6. Ohishi I, Sugii S, Sakaguchi G, (1977) Oral toxicities of Clostridium botulinum toxins in response to molecular size. Infect Immun 16: 107-109.
7. Ohishi I, (1984) Oral toxicities of Clostridium botulinum type A and B toxins from different strains. Infect Immun 43: 487-490.
8. Sakaguchi G, (1982) Clostridium botulinum toxins. Pharmacol Ther 19: 165-194.
9. Hill KK, Smith TJ, (2013) Genetic Diversity Within Clostridium botulinum Serotypes, Botulinum Neurotoxin Gene Clusters and Toxin Subtypes. Curr Top Microbiol Immunol 364: 1-20.
10. Somers E, DasGupta BR, (1991) Clostridium botulinum types A, B, C1, and E produce proteins with or without hemagglutinating activity: do they share common amino acid sequences and genes? J Protein Chem 10: 415-425.
11. Lin G, Tepp WH, Pier CL, Jacobson MJ, Johnson EA, (2010) Expression of the Clostridium botulinum A2 neurotoxin gene cluster proteins and characterization of the A2 complex. Appl Environ Microbiol 76: 40-47.
12. Inoue K, Sobhany M, Transue TR, Oguma K, Pedersen LC, et al. (2003) Structural analysis by X-ray crystallography and calorimetry of a haemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum. Microbiology 149: 3361-3370.
13. Nakamura T, Tonozuka T, Ito S, Takeda Y, Sato R, et al. (2011) Molecular diversity of the two sugar-binding sites of the beta-trefoil lectin HA33/C (HA1) from Clostridium botulinum type C neurotoxin. Arch Biochem Biophys 512: 69-77.
14. Hasegawa K, Watanabe T, Suzuki T, Yamano A, Oikawa T, et al. (2007) A novel subunit structure of clostridium botulinum serotype D toxin complex with three extended arms. J Biol Chem 282: 24777-24783.
15. Nakamura T, Kotani M, Tonozuka T, Ide A, Oguma K, et al. (2009) Crystal structure of the HA3 subcomponent of Clostridium botulinum type C progenitor toxin. J Mol Biol 385: 1193-1206.
16. Yamashita S, Yoshida H, Uchiyama N, Nakakita Y, Nakakita S, et al. (2012) Carbohydrate recognition mechanism of HA70 from Clostridium botulinum deduced from X-ray structures in complexes with sialylated oligosaccharides. FEBS Lett 586: 2404-2410.
17. Arndt JW, Gu J, Jaroszewski L, Schwarzenbacher R, Hanson MA, et al. (2005) The structure of the neurotoxin-associated protein HA33/A from Clostridium botulinum suggests a reoccurring beta-trefoil fold in the progenitor toxin complex. J Mol Biol 346: 1083-1093.
18. Bryant AM, Davis J, Cai S, Singh BR, (2013) Molecular Composition and Extinction Coefficient of Native Botulinum Neurotoxin Complex Produced by Clostridium botulinum Hall A Strain. Protein J 32: 106-117.
19. Lietzow MA, Gielow ET, Le D, Zhang J, Verhagen MF, (2008) Subunit stoichiometry of the Clostridium botulinum type A neurotoxin complex determined using denaturing capillary electrophoresis. Protein J 27: 420-425.
20. Inoue K, Fujinaga Y, Watanabe T, Ohyama T, Takeshi K, et al. (1996) Molecular composition of Clostridium botulinum type A progenitor toxins. Infect Immun 64: 1589-1594.
21. Suzuki T, Watanabe T, Mutoh S, Hasegawa K, Kouguchi H, et al. (2005) Characterization of the interaction between subunits of the botulinum toxin complex produced by serotype D through tryptic susceptibility of the isolated components and complex forms. Microbiology 151: 1475-1483.
22. Benefield DA, Dessain SK, Shine N, Ohi MD, Lacy DB, (2013) Molecular assembly of botulinum neurotoxin progenitor complexes. Proc Natl Acad Sci U S A 110: 5630-5635.
23. Gu S, Jin R, (2013) Assembly and function of the botulinum neurotoxin progenitor complex. Curr Top Microbiol Immunol 364: 21-44.
24. Kojima S, Eguchi H, Ookawara T, Fujiwara N, Yasuda J, et al. (2005) Clostridium botulinum type A progenitor toxin binds to Intestine-407 cells via N-acetyllactosamine moiety. Biochem Biophys Res Commun 331: 571-576.
25. Fujinaga Y, Inoue K, Nomura T, Sasaki J, Marvaud JC, et al. (2000) Identification and characterization of functional subunits of Clostridium botulinum type A progenitor toxin involved in binding to intestinal microvilli and erythrocytes. FEBS Lett 467: 179-183.
26. Inoue K, Fujinaga Y, Honke K, Arimitsu H, Mahmut N, et al. (2001) Clostridium botulinum type A haemagglutinin-positive progenitor toxin (HA(+)-PTX) binds to oligosaccharides containing Gal beta1-4GlcNAc through one subcomponent of haemagglutinin (HA1). Microbiology 147: 811-819.
27. Sugawara Y, Matsumura T, Takegahara Y, Jin Y, Tsukasaki Y, et al. (2010) Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin. J Cell Biol 189: 691-700.
28. Jin Y, Takegahara Y, Sugawara Y, Matsumura T, Fujinaga Y, (2009) Disruption of the epithelial barrier by botulinum haemagglutinin (HA) proteins- differences in cell tropism and the mechanism of action between HA proteins of types A or B, and HA proteins of type C. Microbiology 155: 35-45.
29. Matsumura T, Jin Y, Kabumoto Y, Takegahara Y, Oguma K, et al. (2008) The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption. Cell Microbiol 10: 355-364.
30. Eisele KH, Fink K, Vey M, Taylor HV, (2011) Studies on the dissociation of botulinum neurotoxin type A complexes. Toxicon 57: 555-565.
31. Sagane Y, Watanabe T, Kouguchi H, Sunagawa H, Obata S, et al. (2002) Spontaneous nicking in the nontoxic-nonhemagglutinin component of the Clostridium botulinum toxin complex. Biochem Biophys Res Commun 292: 434-440.
32. Fujita R, Fujinaga Y, Inoue K, Nakajima H, Kumon H, et al. (1995) Molecular characterization of two forms of nontoxic-nonhemagglutinin components of Clostridium botulinum type A progenitor toxins. FEBS Lett 376: 41-44.
33. Ohyama T, Watanabe T, Fujinaga Y, Inoue K, Sunagawa H, et al. (1995) Characterization of nontoxic-nonhemagglutinin component of the two types of progenitor toxin (M and L) produced by Clostridium botulinum type D CB-16. Microbiol Immunol 39: 457-465.
34. Miyata K, Yoneyama T, Suzuki T, Kouguchi H, Inui K, et al. (2009) Expression and stability of the nontoxic component of the botulinum toxin complex. Biochem Biophys Res Commun 384: 126-130.
35. Kouguchi H, Watanabe T, Sagane Y, Sunagawa H, Ohyama T, (2002) In vitro reconstitution of the Clostridium botulinum type D progenitor toxin. J Biol Chem 277: 2650-2656.
36. Hidalgo IJ, Raub TJ, Borchardt RT, (1989) Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 96: 736-749.
37. Grasset E, Pinto M, Dussaulx E, Zweibaum A, Desjeux JF, (1984) Epithelial properties of human colonic carcinoma cell line Caco-2: electrical parameters. Am J Physiol 247: C260-267.
38. Yu D, Marchiando AM, Weber CR, Raleigh DR, Wang Y, et al. (2010) MLCK-dependent exchange and actin binding region-dependent anchoring of ZO-1 regulate tight junction barrier function. Proc Natl Acad Sci U S A 107: 8237-8241.
39. Sambuy Y, De Angelis I, Ranaldi G, Scarino ML, Stammati A, et al. (2005) The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol Toxicol 21: 1-26.
40. Obert G, Peiffer I, Servin AL, (2000) Rotavirus-induced structural and functional alterations in tight junctions of polarized intestinal Caco-2 cell monolayers. J Virol 74: 4645-4651.
41. Canil C, Rosenshine I, Ruschkowski S, Donnenberg MS, Kaper JB, et al. (1993) Enteropathogenic Escherichia coli decreases the transepithelial electrical resistance of polarized epithelial monolayers. Infect Immun 61: 2755-2762.
42. Torgersen ML, Skretting G, van Deurs B, Sandvig K, (2001) Internalization of cholera toxin by different endocytic mechanisms. J Cell Sci 114: 3737-3747.
43. Maksymowych AB, Simpson LL, (1998) Binding and transcytosis of botulinum neurotoxin by polarized human colon carcinoma cells. J Biol Chem 273: 21950-21957.
44. Niwa K, Koyama K, Inoue S, Suzuki T, Hasegawa K, et al. (2007) Role of nontoxic components of serotype D botulinum toxin complex in permeation through a Caco-2 cell monolayer, a model for intestinal epithelium. FEMS Immunol Med Microbiol 49: 346-352.
45. Couesnon A, Pereira Y, Popoff MR, (2008) Receptor-mediated transcytosis of botulinum neurotoxin A through intestinal cell monolayers. Cell Microbiol 10: 375-387.
46. DasGupta BR, Sugiyama H, (1977) Inhibition of Clostridium botulinum types A and B hemagglutinins by sugars. Can J Microbiol 23: 1257-1260.
47. Poppe L, Stuike-Prill R, Meyer B, van Halbeek H, (1992) The solution conformation of sialyl-alpha (2----6)-lactose studied by modern NMR techniques and Monte Carlo simulations. J Biomol NMR 2: 109-136.
48. Gamblin SJ, Haire LF, Russell RJ, Stevens DJ, Xiao B, et al. (2004) The structure and receptor binding properties of the 1918 influenza hemagglutinin. Science 303: 1838-1842.
49. Liu J, Stevens DJ, Haire LF, Walker PA, Coombs PJ, et al. (2009) Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957. Proc Natl Acad Sci U S A 106: 17175-17180.
50. Stevens J, Corper AL, Basler CF, Taubenberger JK, Palese P, et al. (2004) Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science 303: 1866-1870.
51. Nakamura T, Tonozuka T, Ide A, Yuzawa T, Oguma K, et al. (2008) Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin. J Mol Biol 376: 854-867.
52. Fujii N, Kimura K, Yokosawa N, Yashiki T, Tsuzuki K, et al. (1993) The complete nucleotide sequence of the gene encoding the nontoxic component of Clostridium botulinum type E progenitor toxin. J Gen Microbiol 139: 79-86.
53. East AK, Collins MD, (1994) Conserved structure of genes encoding components of botulinum neurotoxin complex M and the sequence of the gene coding for the nontoxic component in nonproteolytic Clostridium botulinum type F. Curr Microbiol 29: 69-77.
54. Ohi M, Li Y, Cheng Y, Walz T, (2004) Negative Staining and Image Classification- Powerful Tools in Modern Electron Microscopy. Biol Proced Online 6: 23-34.
55. Tang G, Peng L, Baldwin PR, Mann DS, Jiang W, et al. (2007) EMAN2: an extensible image processing suite for electron microscopy. J Struct Biol 157: 38-46.
56. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, et al. (2004) UCSF Chimera-a visualization system for exploratory research and analysis. J Comput Chem 25: 1605-1612.
57. Otwinowski Z, Minor W, (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol 276: 307-326.
58. Battye TG, Kontogiannis L, Johnson O, Powell HR, Leslie AG, (2011) iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM. Acta Crystallogr D Biol Crystallogr 67: 271-281.
59. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, et al. (2007) Phaser crystallographic software. J Appl Cryst 40: 658-674.
60. Emsley P, Cowtan K, (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60: 2126-2132.
61. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66: 213-221.
62. Brunger AT, (1992) Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature 355: 472-475.
63. Chen VB, Arendall WB, (2010) MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr 66: 12-21.
64. Hayward S, Berendsen HJ, (1998) Systematic analysis of domain motions in proteins from conformational change: new results on citrate synthase and T4 lysozyme. Proteins 30: 144-154.