Membrane translocation of diphtheria toxin A-fragment: Role of carboxy- terminal region

The C-terminal end of diphtheria toxin A-fragment was altered and the consequences for toxicity and translocation of the A-fragment to the cytosol were studied. Mutations and deletions in the protease-sensitive, disulfide-bridged region linking the two functional parts of the toxin, the A- and B-fragments, reduced the toxicity of the protein as such, but when the mutant toxins were cleaved («nicked») by trypsin before being added to cells, the toxicity was restored. Prevention of disulfide formation by removal of Cys 186 resulted in complete loss of toxicity