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Effect of endosomal acidification on small ion transport through the anthrax toxin PA 63 channel
Author(s) -
Kalu Nnanya,
Alcaraz Antonio,
Yamini Goli,
Momben Abolfath Sanaz,
Lucas Laura,
Kenney Clare,
Aguilella Vicente M.,
Nestorovich Ekaterina M.
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12866
Subject(s) - anthrax toxin , conductance , chemistry , biophysics , endosome , toxin , endocytic cycle , ion transporter , internalization , bacillus anthracis , biochemistry , endocytosis , intracellular , bacteria , cell , biology , membrane , fusion protein , mathematics , combinatorics , gene , recombinant dna , genetics
Tight regulation of pH is critical for the structure and function of cells and organelles. The pH environment changes dramatically along the endocytic pathway, an internalization transport process that is ‘hijacked’ by many intracellularly active bacterial exotoxins, including the anthrax toxin. Here, we investigate the role of pH on single‐channel properties of the anthrax toxin protective antigen ( PA 63 ). Using conductance and current noise analysis, blocker binding, ion selectivity, and poly(ethylene glycol) partitioning measurements, we show that the channel exists in two different open states (‘maximum’ and ‘main’) at pH ≥ 5.5, while only a maximum conductance state is detected at pH < 5.5. We describe two substantially distinct patterns of PA 63 conductance dependence on KCl concentration uncovered at pH 6.5 and 4.5.