title: Domain 4 of the anthrax protective antigen maintains structure and binding to the host receptor CMG2 at low pH.
abstract: 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.
authors.affiliation: Department of Chemistry, Wichita State University, Wichita, Kansas 67226, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Williams
authors.forename: Scott
authors.initials: S
authors.lastname: Lovell
authors.forename: Asokan
authors.initials: A
authors.lastname: Anbanandam
authors.forename: Rahif
authors.initials: R
authors.lastname: El-Chami
authors.forename: James G
authors.initials: JG
authors.lastname: Bann
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002850:Chromatography, Gel; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D018000:Receptors, Peptide; D013050:Spectrometry, Fluorescence; D013696:Temperature; D013816:Thermodynamics
chemical_list: C447150:ANTXR2 protein, human; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008565:Membrane Proteins; D018000:Receptors, Peptide; C030325:anthrax toxin