Abstract
Verotoxin II (VTII: or Shiga-like toxin 2) is a key factor for Escherichia coli O157:H7-induced multiple tissue failure and contains a pentameric sequence (NWGRI) similar to the Bcl-2 homolog domain, BH1. In the current study, we demonstrate that VTII, but not VTI, interacts with Bcl-2 through each BH1 domain pentameric sequence (NWGRI) and that the VTII/Bcl-2 complex is necessary for cell-death induction in target cells. VTII translocates to mitochondria and induces cell death only when target cells are expressing Bcl-2. In addition, interruption of VTII-Bcl-2 complex formation by a pentameric BH1 synthetic peptide suppresses VTII-induced cell death. In the present article, we propose that Bcl-2 mediates VTII-induced target cell death by the interaction with each pentameric sequence of BH1 domain.
MeSH terms
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Amino Acid Sequence
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Bacterial Toxins / chemistry
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Bacterial Toxins / metabolism
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Bacterial Toxins / toxicity*
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Blotting, Western
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Caspase 3
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Caspases / metabolism
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Cell Death*
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Cell Nucleus / metabolism
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Cell Survival / drug effects
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DNA, Mitochondrial / metabolism
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Dimerization
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Dose-Response Relationship, Drug
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Enzyme Activation
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Escherichia coli / metabolism
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Humans
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Microinjections
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Mitochondria / metabolism
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Molecular Sequence Data
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / physiology*
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Sequence Homology, Amino Acid
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Shiga Toxin 1
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Shiga Toxin 2
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Time Factors
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Transfection
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Tumor Cells, Cultured
Substances
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Bacterial Toxins
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DNA, Mitochondrial
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Proto-Oncogene Proteins c-bcl-2
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Shiga Toxin 1
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Shiga Toxin 2
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CASP3 protein, human
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Caspase 3
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Caspases