Involvement of domain 3 in oligomerization by the protective antigen moiety of anthrax toxin.
Protective antigen (PA), a component of anthrax toxin, binds receptors on mammalian cells and is activated by a cell surface protease. The resulting active fragment, PA(63), forms ring-shaped heptamers, binds the enzymic moieties of the toxin, and translocates them to the cytosol. Of the four crystallographic domains of PA, domain 1 has been implicated in binding the enzymic moieties; domain 2 is involved in membrane insertion and oligomerization; and domain 4 binds receptor. To determine the function of domain 3, we developed a screen that allowed us to isolate random mutations that cause defects in the activity of PA. We identified several mutations in domain 3 that affect monomer-monomer interactions in the PA(63) heptamer, indicating that this may be the primary function of this domain.
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
J
J
Mogridge
M
M
Mourez
R J
RJ
Collier
D000818:Animals; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D001704:Biopolymers; D016466:CHO Cells; D006224:Cricetinae; D004587:Electrophoresis, Agar Gel; D008958:Models, Molecular; D009154:Mutation; D010957:Plasmids; D017434:Protein Structure, Tertiary; D012413:Rubidium / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001704:Biopolymers; C030325:anthrax toxin; D012413:Rubidium