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Shiga toxin: purification, structure, and function
A Donohue-Rolfe1, D W Acheson, G T Keusch
1Department of Medicine, New England Medical Center, Boston, Massachusetts 02111.
Abstract:
Shiga toxin is a potent toxin produced by Shigella dysenteriae type 1 strains. The toxin has three biologic activities--cytotoxicity, enterotoxicity, and neurotoxicity--and one known biochemical effect: inhibition of protein synthesis. It consists of two polypeptide chains, an A chain (molecular weight, 32,225) and a B chain (molecular weight, 7,691). These two peptides associate with a stoichiometry of one A and five B subunits to form the holotoxin. The A chain is responsible for the biochemical effect of the holotoxin: cleavage of the N-glycosidic bond of adenine at nucleotide position 4324 in the 28S rRNA of the 60S ribosomal subunit. The B chain mediates binding of toxin to cell surface receptors. Shiga toxin is the prototype of a family of toxin molecules that have been termed Shiga-like in terms of both structural and functional analysis.
Insights
Shiga toxin, produced by Shigella dysenteriae, inhibits protein synthesis by damaging ribosomal RNA. Its structure includes an A chain for enzymatic activity and a B chain for cell binding, defining Shiga-like toxins.
Area of Science:
- Microbiology
- Molecular Biology
- Toxicology
Background:
- Shiga toxin is a potent cytotoxin produced by Shigella dysenteriae type 1.
- It exhibits cytotoxicity, enterotoxicity, and neurotoxicity, primarily by inhibiting protein synthesis.
Purpose of the Study:
- To elucidate the structure-function relationship of Shiga toxin.
- To understand the mechanism of protein synthesis inhibition and cell binding.
Main Methods:
- Biochemical analysis of toxin structure and subunit function.
- Identification of the specific rRNA target and cleavage site.
Main Results:
- Shiga toxin comprises an A chain (32,225 Da) and a B chain (7,691 Da) in a 1:5 stoichiometry.
- The A chain cleaves adenine at nucleotide position 4324 in 28S rRNA, inhibiting protein synthesis.
- The B chain facilitates toxin binding to cell surface receptors.
Conclusions:
- Shiga toxin's mechanism involves specific rRNA cleavage by the A chain and receptor-mediated cell entry via the B chain.
- This toxin serves as a prototype for structurally and functionally similar Shiga-like toxins.