Antigenic Structure of Clostridium Botulinum Type B Neurotoxin and Its Interaction with Gangliosides, Cerebroside, and Free Fatty Acids

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 1987 Dec 1

PMID 2824382

Citations 8

Authors

S Kozaki

J Ogasawara

Y Shimote

Y Kamata

G Sakaguchi

Affiliations

Soon will be listed here.

Abstract

A fragment distinct from the heavy and light chains was obtained by treatment of Clostridium botulinum type B neurotoxin with chymotrypsin. Enzyme-linked immunosorbent assay and immunoblotting analysis with monoclonal antibodies showed that the fragment consisted of the light chain and part of the heavy chain (H-1 fragment) linked together by a disulfide bond. Monoclonal antibodies reacting to the heavy chain but not to the fragment were thought to recognize the epitopes on the remaining portion (H-2 fragment) of the heavy chain, being easily digested by chymotrypsin. Thus, the antigenic structure of type B neurotoxin resembles those of type A and E neurotoxins. The chymotrypsin-induced fragment bound to cerebroside and free fatty acids but not to gangliosides. The manner of binding of type B neurotoxin to gangliosides and free fatty acids was different from those of type A and E neurotoxins. Such differences in the reactivities to lipids may be related to the finding that each neurotoxin binds to a type-specific site on the neural membrane.

Citing Articles

Retargeted clostridial neurotoxins as novel agents for treating chronic diseases.

Yeh F, Zhu Y, Tepp W, Johnson E, Bertics P, Chapman E Biochemistry. 2011; 50(48):10419-21.

PMID: 22047069 PMC: 3226321. DOI: 10.1021/bi201490t.

Analysis of epitope information related to Bacillus anthracis and Clostridium botulinum.

Zarebski L, Vaughan K, Sidney J, Peters B, Grey H, Janda K Expert Rev Vaccines. 2008; 7(1):55-74.

PMID: 18251694 PMC: 3319117. DOI: 10.1586/14760584.7.1.55.

Recombinant derivatives of clostridial neurotoxins as delivery vehicles for proteins and small organic molecules.

Zdanovskaia M, Los G, Zdanovsky A J Protein Chem. 2001; 19(8):699-707.

PMID: 11307955 DOI: 10.1023/a:1007164619921.

Characterization of Clostridium botulinum type B neurotoxin associated with infant botulism in japan.

Kozaki S, Kamata Y, Nishiki T, Kakinuma H, Maruyama H, Takahashi H Infect Immun. 1998; 66(10):4811-6.

PMID: 9746583 PMC: 108594. DOI: 10.1128/IAI.66.10.4811-4816.1998.

Sequence homology between tetanus and botulinum toxins detected by an antipeptide antibody.

Halpern J, Smith L, Seamon K, Groover K, Habig W Infect Immun. 1989; 57(1):18-22.

PMID: 2909486 PMC: 313034. DOI: 10.1128/iai.57.1.18-22.1989.

References

Steinbuch M, Audran R . The isolation of IgG from mammalian sera with the aid of caprylic acid. Arch Biochem Biophys. 1969; 134(2):279-84. DOI: 10.1016/0003-9861(69)90285-9. View

LOWRY O, ROSEBROUGH N, FARR A, RANDALL R . Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75. View

Simpson L, Rapport M . Ganglioside inactivation of botulinum toxin. J Neurochem. 1971; 18(7):1341-3. DOI: 10.1111/j.1471-4159.1971.tb00235.x. View

Dasgupta B, Sugiyama H . A common subunit structure in Clostridium botulinum type A, B and E toxins. Biochem Biophys Res Commun. 1972; 48(1):108-12. DOI: 10.1016/0006-291x(72)90350-6. View

Kozaki S, Sakaguchi S, Sakaguchi G . Purification and some properties of progenitor toxins of Clostridium botulinum type B. Infect Immun. 1974; 10(4):750-6. PMC: 423017. DOI: 10.1128/iai.10.4.750-756.1974. View

Helting T, ZWISLER O . Structure of tetanus toxin. I. Breakdown of the toxin molecule and discrimination between polypeptide fragments. J Biol Chem. 1977; 252(1):187-93. View

Kozaki S, Miyazaki S, Sakaguchi G . Development of antitoxin with each of two complementary fragments of Clostridium botulinum type B derivative toxin. Infect Immun. 1977; 18(3):761-6. PMC: 421300. DOI: 10.1128/iai.18.3.761-766.1977. View

Kozaki S . Interaction of botulinum type A, B and E derivative toxins with synaptosomes of rat brain. Naunyn Schmiedebergs Arch Pharmacol. 1979; 308(1):67-70. DOI: 10.1007/BF00499721. View

Towbin H, Staehelin T, Gordon J . Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979; 76(9):4350-4. PMC: 411572. DOI: 10.1073/pnas.76.9.4350. View

10.

Kitamura M, Iwamori M, Nagai Y . Interaction between Clostridium botulinum neurotoxin and gangliosides. Biochim Biophys Acta. 1980; 628(3):328-35. DOI: 10.1016/0304-4165(80)90382-7. View

11.

Sugiyama H . Clostridium botulinum neurotoxin. Microbiol Rev. 1980; 44(3):419-48. PMC: 373187. DOI: 10.1128/mr.44.3.419-448.1980. View

12.

Simpson L . The origin, structure, and pharmacological activity of botulinum toxin. Pharmacol Rev. 1981; 33(3):155-88. View

13.

Sakaguchi G . Clostridium botulinum toxins. Pharmacol Ther. 1982; 19(2):165-94. DOI: 10.1016/0163-7258(82)90061-4. View

14.

Kondo H, Shimizu T, Kubonoya M, Izumi N, Takahashi M, Sakaguchi G . Titration of botulinum toxins for lethal toxicity by intravenous injection into mice. Jpn J Med Sci Biol. 1984; 37(3):131-5. DOI: 10.7883/yoken1952.37.131. View

15.

Hoch D, Ehrlich B, Finkelstein A, Dasgupta B, Simpson L . Channels formed by botulinum, tetanus, and diphtheria toxins in planar lipid bilayers: relevance to translocation of proteins across membranes. Proc Natl Acad Sci U S A. 1985; 82(6):1692-6. PMC: 397338. DOI: 10.1073/pnas.82.6.1692. View

16.

Schmidt J, Sathyamoorthy V, Dasgupta B . Partial amino acid sequences of botulinum neurotoxins types B and E. Arch Biochem Biophys. 1985; 238(2):544-8. DOI: 10.1016/0003-9861(85)90198-5. View

17.

Shone C, Hambleton P, Melling J . Inactivation of Clostridium botulinum type A neurotoxin by trypsin and purification of two tryptic fragments. Proteolytic action near the COOH-terminus of the heavy subunit destroys toxin-binding activity. Eur J Biochem. 1985; 151(1):75-82. DOI: 10.1111/j.1432-1033.1985.tb09070.x. View

18.

Sathyamoorthy V, Dasgupta B . Separation, purification, partial characterization and comparison of the heavy and light chains of botulinum neurotoxin types A, B, and E. J Biol Chem. 1985; 260(19):10461-6. View

19.

Evans D, Williams R, Shone C, Hambleton P, Melling J, Dolly J . Botulinum neurotoxin type B. Its purification, radioiodination and interaction with rat-brain synaptosomal membranes. Eur J Biochem. 1986; 154(2):409-16. DOI: 10.1111/j.1432-1033.1986.tb09413.x. View

20.

Takamizawa K, Iwamori M, Kozaki S, Sakaguchi G, Tanaka R, Takayama H . TLC immunostaining characterization of Clostridium botulinum type A neurotoxin binding to gangliosides and free fatty acids. FEBS Lett. 1986; 201(2):229-32. DOI: 10.1016/0014-5793(86)80614-7. View