The pH-Dependent Trigger in Diphtheria Toxin T Domain Comes with a Safety Latch.

ABSTRACT: Protein-side-chain protonation, coupled to conformational rearrangements, is one way of regulating physiological function caused by changes in protein environment. Specifically, protonation of histidine residues has been implicated in pH-dependent conformational switching in several systems, including the diphtheria toxin translocation (T) domain, which is responsible for the toxin's cellular entry via the endosomal pathway. Our previous studies a) identified protonation of H257 as a major component of the T domain's conformational switch and b) suggested the possibility of a neighboring H223 acting as a modulator, affecting the protonation of H257 and preventing premature conformational changes outside the endosome. To verify this "safety-latch" hypothesis, we report here the pH-dependent

SUBMITTER: Rodnin MV 

PROVIDER: S-EPMC5103022 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature