Proteolytic Cleavage of Tetanus Toxin Increases Activity

Gregory K. Bergey, William H. Habig, Jeffrey I. Bennett, Clara S. Lin

Research output: Contribution to journalArticlepeer-review

Abstract

Abstract: Tetanus toxin is initially synthesized in the form of a single polypeptide chain and then proteolytically “nicked” by the bacteria to produce a two‐chain structure joined by a disulfide bond. This two‐chain form of the toxin is the form known to be biologically active. Whether such nicking is necessary for activity, as it is for certain other bacterial toxins, has not been demonstrated previously. Single‐chain toxin preparations produced by salt extraction from the bacteria are characterized and compared with pure two‐chain toxin obtained from extracellular filtrates. The ability of these various toxin preparations to produce paroxysmal activity in mouse spinal cord neurons grown in dissociated cell culture is described. The pure two‐chain toxin is demonstrated to have greater activity than the single‐chain toxin preparations. Indeed the activity of the single‐chain toxin preparations can be explained by the small amounts of residual two‐chain toxin present in these extracts. Using a protease from a toxin‐minus strain of Clostridium tetani to convert a single‐chain toxin preparation to two‐chain toxin increases toxin activity. In vivo the single‐chain toxin preparation is also less toxic. These findings indicate that proteolytic nicking of tetanus toxin increases activity. The unnicked, single‐chain form of tetanus toxin may be a relatively nontoxic protoxin form of the toxin; this is a structure‐function relationship similar to that of other bacterial protein toxins.

Original languageEnglish (US)
Pages (from-to)155-161
Number of pages7
JournalJournal of Neurochemistry
Volume53
Issue number1
DOIs
StatePublished - Jul 1989
Externally publishedYes

Keywords

  • Proteolysis
  • Protoxin
  • Spinal cord
  • Tetanus toxin
  • Tissue culture

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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