title: pH dependence and stoichiometry of binding to the Fc region of IgG by the herpes simplex virus Fc receptor gE-gI.
abstract: Herpes simplex virus type 1 encodes two glycoproteins, gE and gI, that form a heterodimer on the surface of virions and infected cells. The gE-gI heterodimer has been implicated in cell-to-cell spread of virus and is a receptor for the Fc fragment of IgG. Previous studies localized the gE-gI-binding site on human IgG to a region near the interface between the C(H)2 and C(H)3 domains of Fc, which also serves as the binding site for bacterial and mammalian Fc receptors. Although there are two potential gE-gI-binding sites per Fc homodimer, only one gE-gI heterodimer binds per IgG in gel filtration experiments. Here we report production of recombinant human Fc molecules that contain zero, one, or two potential gE-gI-binding sites and use them in analytical ultracentrifugation experiments to show that two gE-gI heterodimers can bind to each Fc. Further characterization of the gE-gI interaction with Fc reveals a sharp pH dependence of binding, with K(D) values of approximately 340 and approximately 930 nm for the first and second binding events, respectively, at the slightly basic pH of the cell surface (pH 7.4), but undetectable binding at pH 6.0. This strongly pH-dependent interaction suggests a physiological role for gE-gI dissociation from IgG within acidic intracellular compartments, consistent with a mechanism whereby herpes simplex virus promotes intracellular degradation of anti-viral antibodies.
authors.affiliation: Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Sprague
authors.forename: W Lance
authors.initials: WL
authors.lastname: Martin
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D006224:Cricetinae; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C106607:FCGBP protein, human; D008565:Membrane Proteins; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C044768:glycoprotein E, herpes simplex virus type 1; C064959:glycoprotein I, herpes simplex virus type 1