Structure and function of Clostridium botulinum progenitor toxin

K. Oguma, K. Inoue, Y. Fujinaga, Kenji Yokota, T. Watanabe, T. Ohyama, K. Takeshi, K. Inoue

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Clostridium botulinum strains produce seven immunologically distinct neurotoxins (NTX), type A to G. The NTXs associate with nontoxic components in cultures, and become large complexes with three forms (12S, 16S, and 19S) designated progenitor toxins. The 12S toxin consists of a NTX and a nontoxic component having no hemagglutinin (HA) activity (described here as non-toxic non-HA, NTNH), and the 16S and 19S toxins are formed by conjugation of the 12S toxin with HA. Based on the genetic- and protein chemical-analyses of the progenitor toxins it became clear that 1) the HA consists of four subcomponents namely HA1 (Mr. 33 ~ 35 kDa), HA2 (15 ~ 17 kDa), HA3a (19 ~ 23 kDa), and HA3b (52 ~ 53 kDa), 2) the genes coding for NTX (ntx), NTNH (ntnh), and HA (ha) occur as a cluster; ha lies just upstream of ntnh, and ntx lies just downstream of ntnh, 3) ha is in the opposite orientation from that of ntnh and ntx, 4) ha consists of three ORFs (ha1, ha2, and ha3), 5) the gene product (70 kDa) of ha3 is split into HA3a and HA3b after translation, 6) HA3a is cleaved at several different sites of its N-terminal region to form proteins with slightly different Mrs, 7) the 19S toxin is a dimer of 16S toxin crosslinked by HA1, 8) The NTNHs of type A to D 12S toxins have a cleavage(s) on their N-terminal regions. It also became clear that the HA plays an important role when the 16S (and 19S) toxin is absorbed from the small intestine.

Original languageEnglish
Pages (from-to)17-34
Number of pages18
JournalJournal of Toxicology - Toxin Reviews
Volume18
Issue number1
Publication statusPublished - 1999

Fingerprint

Clostridium
Botulinum Toxins
Hemagglutinins
Neurotoxins
Genes
Clostridium botulinum
Dimers
Open Reading Frames
Small Intestine
Proteins

Keywords

  • Botulinum toxin
  • Clostridium botulinum
  • Hemaggulutinin
  • Progenitor toxin
  • Toxin gene

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Toxicology

Cite this

Oguma, K., Inoue, K., Fujinaga, Y., Yokota, K., Watanabe, T., Ohyama, T., ... Inoue, K. (1999). Structure and function of Clostridium botulinum progenitor toxin. Journal of Toxicology - Toxin Reviews, 18(1), 17-34.

Structure and function of Clostridium botulinum progenitor toxin. / Oguma, K.; Inoue, K.; Fujinaga, Y.; Yokota, Kenji; Watanabe, T.; Ohyama, T.; Takeshi, K.; Inoue, K.

In: Journal of Toxicology - Toxin Reviews, Vol. 18, No. 1, 1999, p. 17-34.

Research output: Contribution to journalArticle

Oguma, K, Inoue, K, Fujinaga, Y, Yokota, K, Watanabe, T, Ohyama, T, Takeshi, K & Inoue, K 1999, 'Structure and function of Clostridium botulinum progenitor toxin', Journal of Toxicology - Toxin Reviews, vol. 18, no. 1, pp. 17-34.
Oguma K, Inoue K, Fujinaga Y, Yokota K, Watanabe T, Ohyama T et al. Structure and function of Clostridium botulinum progenitor toxin. Journal of Toxicology - Toxin Reviews. 1999;18(1):17-34.
Oguma, K. ; Inoue, K. ; Fujinaga, Y. ; Yokota, Kenji ; Watanabe, T. ; Ohyama, T. ; Takeshi, K. ; Inoue, K. / Structure and function of Clostridium botulinum progenitor toxin. In: Journal of Toxicology - Toxin Reviews. 1999 ; Vol. 18, No. 1. pp. 17-34.
@article{c9209c5fcfec4d5892db76e55bb66538,
title = "Structure and function of Clostridium botulinum progenitor toxin",
abstract = "Clostridium botulinum strains produce seven immunologically distinct neurotoxins (NTX), type A to G. The NTXs associate with nontoxic components in cultures, and become large complexes with three forms (12S, 16S, and 19S) designated progenitor toxins. The 12S toxin consists of a NTX and a nontoxic component having no hemagglutinin (HA) activity (described here as non-toxic non-HA, NTNH), and the 16S and 19S toxins are formed by conjugation of the 12S toxin with HA. Based on the genetic- and protein chemical-analyses of the progenitor toxins it became clear that 1) the HA consists of four subcomponents namely HA1 (Mr. 33 ~ 35 kDa), HA2 (15 ~ 17 kDa), HA3a (19 ~ 23 kDa), and HA3b (52 ~ 53 kDa), 2) the genes coding for NTX (ntx), NTNH (ntnh), and HA (ha) occur as a cluster; ha lies just upstream of ntnh, and ntx lies just downstream of ntnh, 3) ha is in the opposite orientation from that of ntnh and ntx, 4) ha consists of three ORFs (ha1, ha2, and ha3), 5) the gene product (70 kDa) of ha3 is split into HA3a and HA3b after translation, 6) HA3a is cleaved at several different sites of its N-terminal region to form proteins with slightly different Mrs, 7) the 19S toxin is a dimer of 16S toxin crosslinked by HA1, 8) The NTNHs of type A to D 12S toxins have a cleavage(s) on their N-terminal regions. It also became clear that the HA plays an important role when the 16S (and 19S) toxin is absorbed from the small intestine.",
keywords = "Botulinum toxin, Clostridium botulinum, Hemaggulutinin, Progenitor toxin, Toxin gene",
author = "K. Oguma and K. Inoue and Y. Fujinaga and Kenji Yokota and T. Watanabe and T. Ohyama and K. Takeshi and K. Inoue",
year = "1999",
language = "English",
volume = "18",
pages = "17--34",
journal = "Toxin Reviews",
issn = "1556-9543",
publisher = "Informa Healthcare",
number = "1",

}

TY - JOUR

T1 - Structure and function of Clostridium botulinum progenitor toxin

AU - Oguma, K.

AU - Inoue, K.

AU - Fujinaga, Y.

AU - Yokota, Kenji

AU - Watanabe, T.

AU - Ohyama, T.

AU - Takeshi, K.

AU - Inoue, K.

PY - 1999

Y1 - 1999

N2 - Clostridium botulinum strains produce seven immunologically distinct neurotoxins (NTX), type A to G. The NTXs associate with nontoxic components in cultures, and become large complexes with three forms (12S, 16S, and 19S) designated progenitor toxins. The 12S toxin consists of a NTX and a nontoxic component having no hemagglutinin (HA) activity (described here as non-toxic non-HA, NTNH), and the 16S and 19S toxins are formed by conjugation of the 12S toxin with HA. Based on the genetic- and protein chemical-analyses of the progenitor toxins it became clear that 1) the HA consists of four subcomponents namely HA1 (Mr. 33 ~ 35 kDa), HA2 (15 ~ 17 kDa), HA3a (19 ~ 23 kDa), and HA3b (52 ~ 53 kDa), 2) the genes coding for NTX (ntx), NTNH (ntnh), and HA (ha) occur as a cluster; ha lies just upstream of ntnh, and ntx lies just downstream of ntnh, 3) ha is in the opposite orientation from that of ntnh and ntx, 4) ha consists of three ORFs (ha1, ha2, and ha3), 5) the gene product (70 kDa) of ha3 is split into HA3a and HA3b after translation, 6) HA3a is cleaved at several different sites of its N-terminal region to form proteins with slightly different Mrs, 7) the 19S toxin is a dimer of 16S toxin crosslinked by HA1, 8) The NTNHs of type A to D 12S toxins have a cleavage(s) on their N-terminal regions. It also became clear that the HA plays an important role when the 16S (and 19S) toxin is absorbed from the small intestine.

AB - Clostridium botulinum strains produce seven immunologically distinct neurotoxins (NTX), type A to G. The NTXs associate with nontoxic components in cultures, and become large complexes with three forms (12S, 16S, and 19S) designated progenitor toxins. The 12S toxin consists of a NTX and a nontoxic component having no hemagglutinin (HA) activity (described here as non-toxic non-HA, NTNH), and the 16S and 19S toxins are formed by conjugation of the 12S toxin with HA. Based on the genetic- and protein chemical-analyses of the progenitor toxins it became clear that 1) the HA consists of four subcomponents namely HA1 (Mr. 33 ~ 35 kDa), HA2 (15 ~ 17 kDa), HA3a (19 ~ 23 kDa), and HA3b (52 ~ 53 kDa), 2) the genes coding for NTX (ntx), NTNH (ntnh), and HA (ha) occur as a cluster; ha lies just upstream of ntnh, and ntx lies just downstream of ntnh, 3) ha is in the opposite orientation from that of ntnh and ntx, 4) ha consists of three ORFs (ha1, ha2, and ha3), 5) the gene product (70 kDa) of ha3 is split into HA3a and HA3b after translation, 6) HA3a is cleaved at several different sites of its N-terminal region to form proteins with slightly different Mrs, 7) the 19S toxin is a dimer of 16S toxin crosslinked by HA1, 8) The NTNHs of type A to D 12S toxins have a cleavage(s) on their N-terminal regions. It also became clear that the HA plays an important role when the 16S (and 19S) toxin is absorbed from the small intestine.

KW - Botulinum toxin

KW - Clostridium botulinum

KW - Hemaggulutinin

KW - Progenitor toxin

KW - Toxin gene

UR - http://www.scopus.com/inward/record.url?scp=0033052084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033052084&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0033052084

VL - 18

SP - 17

EP - 34

JO - Toxin Reviews

JF - Toxin Reviews

SN - 1556-9543

IS - 1

ER -