Anthrax protective antigen forms oligomers during intoxication of mammalian cells

The protective antigen component (PA) of anthrax toxin binds to receptors on target cells and conveys the toxin's edema factor (EF) and lethal factor (LF) components into the cytoplasm. PA (83 kDa) is processed by a cellular protease, yielding a 63-kDa fragment (PA63), which binds EF and/or LF....

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Bibliographic Details
Published in:The Journal of biological chemistry 1994-08, Vol.269 (32), p.20607-20612
Main Authors: MILNE, J. C, FURLONG, D, HANNA, P. C, WALL, J. S, COLLIER, R. J
Format: Article
Language:English
Subjects:
Animals
Antigens, Bacterial
Bacillus anthracis
Bacillus anthracis - chemistry
Bacterial Toxins - chemistry
Bacterial Toxins - toxicity
Bacteriology
Biological and medical sciences
Biological Transport
Biopolymers
CHO Cells
Cricetinae
Electrophoresis, Polyacrylamide Gel
Fundamental and applied biological sciences. Psychology
Hydrogen-Ion Concentration
Microbiology
Microscopy, Electron
Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains
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Summary:The protective antigen component (PA) of anthrax toxin binds to receptors on target cells and conveys the toxin's edema factor (EF) and lethal factor (LF) components into the cytoplasm. PA (83 kDa) is processed by a cellular protease, yielding a 63-kDa fragment (PA63), which binds EF and/or LF. When exposed to acidic pH, PA63 inserts into membranes and forms ion-conductive channels. By electron microscopy, a significant fraction of purified PA63 was found to be in the form of a multi-subunit ring-shaped oligomer (outer diameter, 10.4 nm). The rings are heptameric, as judged by inspection and by rotational power spectra. Purified PA63 showed a high M(r) band, apparently corresponding to the oligomer, on SDS-polyacrylamide gels, and oligomer of similar size was formed in cells in a time-dependent manner after addition of full-length PA. Inhibitors of internalization and endosome acidification blocked conversion of cell-associated PA to a high molecular weight species, and medium at pH 5.0 induced oligomer formation in the presence or absence of the inhibitors. These results correlate PA63 oligomerization with conditions required for translocation of EF and LF across lipid bilayers, implying that the PA63 oligomer may function in translocation.
ISSN:0021-9258
1083-351X
DOI:10.1016/s0021-9258(17)32036-7