The channel formed in planar lipid bilayers by the protective antigen component of anthrax toxin.
Anthrax toxin consists of three proteins: edema factor (EF, 89 kDa), lethal factor (LF, 90 kDa), and protective antigen (PA, 83 kDa). The former two gain access to the cytosol, where they exert their respective toxic effects on a cell, only in binary combination with PA. The proposed pathways of EF and LF transport consists of (i) PA attaching to a membrane receptor; (ii) its proteolytic cleavage into two fragments, of which the larger, 63 kDa piece (PA63) remains attached to the receptor; (iii) either EF or LF binding to PA63; (iv) the complex undergoing endocytosis, and EF or LF being translocated into the cytosol from an acidic vesicle compartment. In planar phospholipid bilayers, PA63 (but not whole PA) forms cation-selection channels; the channel-forming activity of PA63 dramatically increases when the pH of the solution to which it was added is lowered. Tetraalkylammonium ions block the PA63 channel by binding to a site within the channel lumen. Analysis of this blocking phenomenon reveals that these ions can pass through the channel from one side of the membrane to the other and that the diameter of the channel is about 12 A. The N-terminal 30 kDa end of EF, which contains the region of EF that binds to PA63, interacts with the PA63 channel in a voltage-dependent manner. The nature of the voltage-gating suggests that this binding fragment of EF can enter and block the channel and even pass through it, but further evidence will be required to establish this.
Finkelstein
A
A
Department of Physiology, Albert Einstein College of Medicine, Bronx, NY 10461.
D000881:Anthrax / Q000209:etiology; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D007473:Ion Channels / Q000502:physiology*; D008051:Lipid Bilayers / Q000378:metabolism*
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007473:Ion Channels; D008051:Lipid Bilayers; C030325:anthrax toxin