Crucial role of H322 in folding of the diphtheria toxin T-domain into the open-channel state.

ABSTRACT: The translocation (T) domain plays a key role in the entry of diphtheria toxin into the cell. Upon endosomal acidification, the T-domain undergoes a series of conformational changes that lead to its membrane insertion and formation of a channel. Recently, we have reported that the triple replacement of C-terminal histidines H322, H323, and H372 with glutamines prevents the formation of open channels in planar lipid bilayers. Here, we report that this effect is primarily due to the mutation of H322. We further examine the relationship between the loss of functionality and membrane folding in a series of mutants with C-terminal histidine substitutions using spectroscopic assays. The membrane insertion pathway for the mutants differs from that of the wild type as revealed by the membrane-indu

SUBMITTER: Vargas-Uribe M 

PROVIDER: S-EPMC3772984 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature