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Proteolytic cleavage of tetanus toxin increases activity
G K Bergey1, W H Habig, J I Bennett
1Department of Neurology, University of Maryland School of Medicine, Baltimore 21201.
Journal of Neurochemistry
|July 1, 1989
Summary
Proteolytic nicking of tetanus toxin into a two-chain structure is essential for its biological activity. The single-chain form acts as a protoxin, requiring cleavage to become fully toxic.
Area of Science:
- Neuroscience
- Microbiology
- Biochemistry
Background:
- Tetanus toxin is initially synthesized as a single chain.
- Proteolytic nicking converts it to an active two-chain form.
- The necessity of this nicking for tetanus toxin activity was previously unproven.
Purpose of the Study:
- To investigate the necessity of proteolytic nicking for tetanus toxin activity.
- To compare the biological activity of single-chain and two-chain tetanus toxin.
- To characterize the structure-function relationship of tetanus toxin.
Main Methods:
- Characterization of single-chain toxin from salt extracts.
- Comparison with purified two-chain toxin from filtrates.
- Assessment of neurotoxic activity in mouse spinal cord neuron cultures.
- In vivo toxicity studies.
Main Results:
- Pure two-chain tetanus toxin exhibited significantly greater activity than single-chain preparations.
- The observed activity of single-chain toxin was attributable to residual two-chain toxin.
- Conversion of single-chain to two-chain toxin by bacterial protease increased activity.
- Single-chain toxin demonstrated reduced toxicity in vivo.
Conclusions:
- Proteolytic nicking is crucial for increasing tetanus toxin activity.
- The single-chain form of tetanus toxin functions as a relatively nontoxic protoxin.
- This structure-function relationship is consistent with other bacterial protein toxins.