title: Bivalent binding of IgA1 to FcalphaRI suggests a mechanism for cytokine activation of IgA phagocytosis.
abstract: FcalphaRI, the receptor specific for the Fc region of immunoglobulin A (IgA), is responsible for IgA-mediated phagocytosis, oxidative burst, and antibody-dependent cellular cytotoxicity. Using the techniques of analytical ultracentrifugation and equilibrium gel-filtration, we show that two FcalphaRI molecules bind to a single Fcalpha homodimer. Surface plasmon resonance studies confirm the 2:1 stoichiometry of binding, with equilibrium dissociation constants of 176 nM and 431 nM for the first and second binding events, respectively. The binding affinity decreases at acidic pH in a manner consistent with protonation of a single histidine residue in the binding site. A thermodynamic analysis indicates that the histidine residue does not participate in a salt-bridge in the complex; in fact, less than 10% of the free energy of binding was contributed by electrostatic interactions. The bivalent, pH-dependent interaction between FcalphaRI and IgA has important implications for cytokine-dependent phagocytosis of IgA and the FcalphaRI-mediated degradation or recycling of IgA.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Herr
authors.forename: Clinton L
authors.initials: CL
authors.lastname: White
authors.forename: Christina
authors.initials: C
authors.lastname: Milburn
authors.forename: Carol
authors.initials: C
authors.lastname: Wu
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
mesh_terms: D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002850:Chromatography, Gel; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D005822:Genetic Vectors; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007070:Immunoglobulin A / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D010587:Phagocytosis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011961:Receptors, Fc / Q000737:chemistry* / Q000378:metabolism; D020349:Surface Plasmon Resonance; D013816:Thermodynamics; D013997:Time Factors; D014162:Transfection; D014461:Ultracentrifugation
chemical_list: D015703:Antigens, CD; D016207:Cytokines; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc; D006639:Histidine