Characterization of the functional activity of botulinum neurotoxin subtype B6

Tomoko Kohda, Keiji Nakamura, Koji Hosomi, Yasushi Torii, Shunji Kozaki, Masafumi Mukamoto

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Clostridium botulinum produces the highly potent neurotoxin, botulinum neurotoxin (BoNT), which is classified into seven serotypes (A–G); the subtype classification is confirmed by the diversity of amino acid sequences among the serotypes. BoNT from the Osaka05 strain is associated with type B infant botulism and has been classified as BoNT/B subtype B6 (BoNT/B6) by phylogenetic analysis and the antigenicity of its C-terminal heavy chain (HC) domain. However, the molecular bases for its properties, including its potency, are poorly understood. In this study, BoNT/B6 holotoxin was purified and the biological activity and receptor binding activity of BoNT/B6 compared with those of the previously-characterized BoNT/B1 and BoNT/B2 subtypes. The derivative BoNT/B6 was found to be already nicked and in an activated form, indicating that endogenous protease production may be higher in this strain than in the other two strains. BoNT/B1 exhibited the greatest lethal activity in mice, followed by BoNT/B6, which is consistent with the sensitivity of PC12 cells. No significant differences were seen in the enzymatic activities of the BoNT/Bs against their substrate. HC/B1 and HC/B6 exhibited similar binding affinities to synaptotagmin II (SytII), which is a specific protein receptor for BoNT/B. Binding to the SytII/ganglioside complex is functionally related to the toxic action; however, the receptor recognition sites are conserved. These results suggest that the distinct characteristics and differences in biological sensitivity of BoNT/B6 may be attributable to the function of its Hc.domain.

Original languageEnglish
Pages (from-to)482-489
Number of pages8
JournalMICROBIOLOGY and IMMUNOLOGY
Volume61
Issue number11
DOIs
Publication statusPublished - Nov 2017

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Virology

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