Structure of the Diphtheria Toxin at Acidic pH: Implications for the Conformational Switching of the Translocation Domain.

ABSTRACT: Diphtheria toxin, an exotoxin secreted by Corynebacterium that causes disease in humans by inhibiting protein synthesis, enters the cell via receptor-mediated endocytosis. The subsequent endosomal acidification triggers a series of conformational changes, resulting in the refolding and membrane insertion of the translocation (T-)domain and ultimately leading to the translocation of the catalytic domain into the cytoplasm. Here, we use X-ray crystallography along with circular dichroism and fluorescence spectroscopy to gain insight into the mechanism of the early stages of pH-dependent conformational transition. For the first time, we present the high-resolution structure of the diphtheria toxin at a mildly acidic pH (5-6) and compare it to the structure at neutral pH (7). We demonst

SUBMITTER: Rodnin MV 

PROVIDER: S-EPMC7695028 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature