Constant-pH MD simulations of the protonation-triggered conformational switching in diphtheria toxin translocation domain.

ABSTRACT: Protonation of key residues in the diphtheria toxin translocation (T)-domain triggered by endosomal acidification is critical for inducing a series of conformational transitions critical for the cellular entry of the toxin. Previous experiments revealed the importance of histidine residues in modulating pH-dependent transitions. They suggested the presence of a "safety latch" preventing premature refolding of the T-domain by a yet poorly understood mechanism. Here, we used constant-pH molecular dynamics simulations to systematically investigate the protonation sequence in the wild-type T-domain and the following mutants: H223Q, H257Q, E259Q, and H223Q/H257Q. Comparison of these computational results with previous experimental data on T-domain stability and activity with the H-to-Q replacem

SUBMITTER: Oliveira NFB 

PROVIDER: S-EPMC11700360 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature