Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation.

Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.

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.

PMID: 15326297 [PubMed - indexed for MEDLINE]

PMCID: PMC516539