Domain 4 of the anthrax protective antigen maintains structure and binding to the host receptor CMG2 at low pH

Protein Sci. 2009 Nov;18(11):2277-86. doi: 10.1002/pro.238.


Domain 4 of the anthrax protective antigen (PA) plays a key role in cellular receptor recognition as well as in pH-dependent pore formation. We present here the 1.95 A crystal structure of domain 4, which adopts a fold that is identical to that observed in the full-length protein. We have also investigated the structural properties of the isolated domain 4 as a function of pH, as well as the pH-dependence on binding to the von Willebrand factor A domain of capillary morphogenesis protein 2 (CMG2). Our results provide evidence that the isolated domain 4 maintains structure and interactions with CMG2 at pH 5, a pH that is known to cause release of the receptor on conversion of the heptameric prepore (PA(63))(7) to a membrane-spanning pore. Our results suggest that receptor release is not driven solely by a pH-induced unfolding of domain 4.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / metabolism*
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism*
  • Chromatography, Gel
  • Circular Dichroism
  • Humans
  • Hydrogen-Ion Concentration
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Stability
  • Protein Structure, Tertiary
  • Receptors, Peptide
  • Spectrometry, Fluorescence
  • Temperature
  • Thermodynamics


  • ANTXR2 protein, human
  • Antigens, Bacterial
  • Bacterial Toxins
  • Membrane Proteins
  • Receptors, Peptide
  • anthrax toxin

Associated data

  • PDB/3INO