Histidine Protonation and Conformational Switching in Diphtheria Toxin Translocation Domain.

ABSTRACT: Protonation of key histidine residues has been long implicated in the acid-mediated cellular action of the diphtheria toxin translocation (T-) domain, responsible for the delivery of the catalytic domain into the cell. Here, we use a combination of computational (constant-pH Molecular Dynamics simulations) and experimental (NMR, circular dichroism, and fluorescence spectroscopy along with the X-ray crystallography) approaches to characterize the initial stages of conformational change happening in solution in the wild-type T-domain and in the H223Q/H257Q double mutant. This replacement suppresses the acid-induced transition, resulting in the retention of a more stable protein structure in solutions at pH 5.5 and, consequently, in reduced membrane-disrupting activity. Here, for the first ti

SUBMITTER: Rodnin MV 

PROVIDER: S-EPMC10467104 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature