Abstract
Diphtheria toxin (DT), a 63,000-molecular weight soluble protein, is toxic to most mammalian cells. The mechanism of intoxication involves a step in which one part of the molecule inserts into a membrane, facilitating the transport of the enzymatic fragment of the protein into the cytoplasm1,2. This event requires an acidic environment and seems to occur at the membrane of an endocytic vesicle3,4. Different cell lines and species differ in their sensitivities to DT—this is due at least in part to differences in the number of DT surface receptors on the cells5, but may also arise from differences in the membrane transport step. It is generally recognized that protein–lipid interactions are of critical importance in membrane transport phenomena (see ref. 6). Thus, it is of interest to determine whether the interaction of DT with membranes is modulated by their composition. We have shown previously that DT interacts with planar lipid bilayers at acidic pH to produce voltage-dependent channels7. We report here that this interaction of DT with bilayers depends on membrane phospholipid composition; the interaction is optimal when inositides are present within the membrane, and the inositides are required on the side of the membrane opposite to that in which DT is introduced.
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Donovan, J., Simon, M. & Montal, M. Insertion of diphtheria toxin into and across membranes: role of phosphoinositide asymmetry. Nature 298, 669–672 (1982). https://doi.org/10.1038/298669a0
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DOI: https://doi.org/10.1038/298669a0
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