Replacement of C-terminal histidines uncouples membrane insertion and translocation in diphtheria toxin T-domain.

ABSTRACT: The translocation (T) domain plays a key role in the action of diphtheria toxin and is responsible for transferring the N-terminus-attached catalytic domain across the endosomal membrane into the cytosol in response to acidification. The T-domain undergoes a series of pH-triggered conformational changes that take place in solution and on the membrane interface, and ultimately result in transbilayer insertion and N-terminus translocation. Structure-function studies along this pathway have been hindered because the protein population occupies multiple conformations at the same time. Here we report that replacement of the three C-terminal histidine residues, H322, H323, and H372, in triple-R or triple-Q mutants prevents effective translocation of the N-terminus. Introduction of these mutation

SUBMITTER: Rodnin MV 

PROVIDER: S-EPMC3218347 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature