Open AccessAnthrax toxin: channel-forming activity of protective antigen in planar phospholipid bilayers.
Author(s) -
Robert O. Blaustein,
Theresa M. Koehler,
R. John Collier,
Alan Finkelstein
Publication year - 1989
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.86.7.2209
Subject(s) - anthrax toxin , diphtheria toxin , endocytosis , toxin , pore forming toxin , chemistry , phospholipid , biophysics , lipid bilayer , cytosol , trypsin , membrane , biochemistry , microbiology and biotechnology , biology , receptor , microbial toxins , fusion protein , enzyme , gene , recombinant dna
The three separate proteins that make up anthrax toxin--protective antigen (PA), edema factor (EF), and lethal factor (LF)--act in binary combinations to produce two distinct reactions in experimental animals: edema (PA + EF) and death (PA + LF). PA is believed to interact with a membrane receptor, and after proteolytic processing, to mediate endocytosis and subsequent translocation of EF or LF into the cytosol. PA can be separated, after mild trypsinolysis, into two fragments, PA65 (65 kDa) and PA20 (20 kDa). We demonstrate that trypsin-cleaved PA is capable of forming cation-selective channels in planar phospholipid bilayer membranes and that this activity is confined to the PA65 fragment; PA20, LF, and EF are devoid of channel-forming activity. These PA65 channels exhibit pH-dependent and voltage-dependent activity--a property reminiscent of the channels formed by the two-chain proteins diphtheria, tetanus, and botulinum toxins.