Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation.
After binding to cellular receptors and proteolytic activation, the protective antigen component of anthrax toxin forms a heptameric prepore. The prepore later undergoes pH-dependent conversion to a pore, mediating translocation of the edema and lethal factors to the cytosol. We describe structures of the prepore (3.6 A) and a prepore:receptor complex (4.3 A) that reveal the location of pore-forming loops and an unexpected interaction of the receptor with the pore-forming domain. Lower pH is required for prepore-to-pore conversion in the presence of the receptor, indicating that this interaction regulates pH-dependent pore formation. We present an example of a receptor negatively regulating pH-dependent membrane insertion.
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
D Borden
DB
Lacy
Darran J
DJ
Wigelsworth
Roman A
RA
Melnyk
Stephen C
SC
Harrison
R John
RJ
Collier
D000942:Antigens, Bacterial / Q000737:chemistry* / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D018000:Receptors, Peptide / Q000737:chemistry* / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018000:Receptors, Peptide; C030325:anthrax toxin; C070309:anthrax toxin receptors