Effect of the Endosomal Acidification on Small Ion Transport Through the Anthrax Toxin PA63 Channel

Abstract

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 singlechannel properties of the anthrax toxin channel, PA 63 . Using conductance and current noise analysis, blocker binding, ion selectivity, and PEG 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.