PH-triggered conformational switching of the diphtheria toxin T-domain: the roles of N-terminal histidines.

ABSTRACT: pH-induced conformational switching is essential for functioning of diphtheria toxin, which undergoes a membrane insertion/translocation transition triggered by endosomal acidification as a key step of cellular entry. In order to establish the sequence of molecular rearrangements and side-chain protonation accompanying the formation of the membrane-competent state of the toxin's translocation (T) domain, we have developed and applied an integrated approach that combines multiple techniques of computational chemistry [e.g., long-microsecond-range, all-atom molecular dynamics (MD) simulations; continuum electrostatics calculations; and thermodynamic integration (TI)] with several experimental techniques of fluorescence spectroscopy. TI calculations indicate that protonation of H257 causes th

SUBMITTER: Kurnikov IV 

PROVIDER: S-EPMC3782538 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature