Anthrax toxin: channel-forming activity of protective antigen in planar phospholipid bilayers.
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.
Blaustein
R O
RO
Department of Physiology, Albert Einstein College of Medicine, Bronx, NY 10461.
Koehler
T M
TM
Collier
R J
RJ
Finkelstein
A
A
D000942:Antigens, Bacterial / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology / Q000302:isolation & purification; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D008051:Lipid Bilayers; D008962:Models, Theoretical; D010713:Phosphatidylcholines
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007473:Ion Channels; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; C030325:anthrax toxin; C021016:1,2-diphytanoylphosphatidylcholine