Translocation domain of botulinum neurotoxin A subtype 2 potently induces entry into neuronal cells

Tomoko Kohda, Kentaro Tsukamoto, Yasushi Torii, Shunji Kozaki, Masafumi Mukamoto

研究成果: Article査読

抄録

Botulinum neurotoxin (BoNT) is the causative agent of botulism in humans and animals. Only BoNT serotype A subtype 1 (BoNT/A1) is used clinically because of its high potency and long duration of action. BoNT/A1 and BoNT/A subtype 2 (BoNT/A2) have a high degree of amino acid sequence similarity in the light chain (LC) (96%), whereas their N-and C-terminal heavy chain (HN and HC) differ by 13%. The LC acts as a zinc-dependent endopeptidase, HN as the translocation domain, and HC as the receptor-binding domain. BoNT/A2 and BoNT/A1 had similar potency in the mouse bioassay, but BoNT/A2 entered faster and more efficiently into neuronal cells. To identify the domains responsible for these characteristics, HN of BoNT/A1 and BoNT/A2 was exchanged to construct chimeric BoNT/A121 and BoNT/A212. After expression in Escherichia coli, chimeric and wild-type BoNT/As were purified as single-chain proteins and activated by conversion to disulfide-linked dichains. The toxicities of recombinant wild-type and chimeric BoNT/As were similar, but dropped to 60% compared with the values of native BoNT/As. The relative orders of SNAP-25 cleavage activity in neuronal cells and toxicity differed. BoNT/A121 and recombinant BoNT/A2 have similar SNAP-25 cleavage activity. BoNT/A2 HN is possibly responsible for the higher potency of BoNT/A2 than BoNT/A1.

本文言語English
ページ(範囲)502-511
ページ数10
ジャーナルMICROBIOLOGY and IMMUNOLOGY
64
7
DOI
出版ステータスPublished - 01-07-2020

All Science Journal Classification (ASJC) codes

  • 微生物学
  • 免疫学
  • ウイルス学

フィンガープリント

「Translocation domain of botulinum neurotoxin A subtype 2 potently induces entry into neuronal cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル