Role of acidic residues in helices TH8-TH9 in membrane interactions of the diphtheria toxin T domain.

ABSTRACT: The pH-triggered membrane insertion of the diphtheria toxin translocation domain (T domain) results in transferring the catalytic domain into the cytosol, which is relevant to potential biomedical applications as a cargo-delivery system. Protonation of residues is suggested to play a key role in the process, and residues E349, D352 and E362 are of particular interest because of their location within the membrane insertion unit TH8-TH9. We have used various spectroscopic, computational and functional assays to characterize the properties of the T domain carrying the double mutation E349Q/D352N or the single mutation E362Q. Vesicle leakage measurements indicate that both mutants interact with the membrane under less acidic conditions than the wild-type. Thermal unfolding and fluorescence mea

SUBMITTER: Ghatak C 

PROVIDER: S-EPMC4417968 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature