pH-Dependent membrane interactions of diphtheria toxin: A genetic approach.
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Date
1990-09
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Abstract
A genetic approach is described for exploring the mechanism by which diphtheria
toxin undergoes pH-dependent membrane insertion and transfer of its enzymic
A fragment into the cytoplasm of mammalian cells. The cloned toxin expressed in
Escherichia coli is secreted to the periplasmic space, where it is processed normally and
folds into a native structure. When bacteria synthesizing the toxin are exposed to pH 5,
they die rapidly. The toxin undergoes a conformational change that is believed to allow it
to be inserted into the bacterial inner membrane and form channels, which proves lethal
for the cell. The membrane insertion event mimics the process by which the toxin inserts
into the endosomal membrane of mammalian cells, leading to release of the enzymic A
fragment into the cytoplasm. The observation of pH-dependent bacterial lethality provides
the basis for a positive genetic selection method for mutant forms of the toxin that are
altered in ability to undergo membrane insertion or pore formation.
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Keywords
Diphtheria toxin, enzymic A, pH-dependent lethality
Citation
Collier R John. pH-Dependent membrane interactions of diphtheria toxin: A genetic approach. Journal of Biosciences. 1990 Sep; 15(3): 169-171.