title: The human cytomegalovirus Fc receptor gp68 binds the Fc CH2-CH3 interface of immunoglobulin G.
abstract: Recognition of immunoglobulin G (IgG) by surface receptors for the Fc domain of immunoglobulin G (Fcgamma), FcgammaRs, can trigger both humoral and cellular immune responses. Two human cytomegalovirus (HCMV)-encoded type I transmembrane receptors with Fcgamma-binding properties (vFcgammaRs), gp34 and gp68, have been identified on the surface of HCMV-infected cells and are assumed to confer protection against IgG-mediated immunity. Here we show that Fcgamma recognition by both vFcgammaRs occurs independently of N-linked glycosylation of Fcgamma, in contrast with the properties of host FcgammaRs. To gain further insight into the interaction with Fcgamma, truncation mutants of the vFcgammaR gp68 ectodomain were probed for Fcgamma binding, resulting in localization of the Fcgamma binding site on gp68 to residues 71 to 289, a region including an immunoglobulin-like domain. Gel filtration and biosensor binding experiments revealed that, unlike host FcgammaRs but similar to the herpes simplex virus type 1 (HSV-1) Fc receptor gE-gI, gp68 binds to the C(H)2-C(H)3 interdomain interface of the Fcgamma dimer with a nanomolar affinity and a 2:1 stoichiometry. Unlike gE-gI, which binds Fcgamma at the slightly basic pH of the extracellular milieu but not at the acidic pH of endosomes, the gp68/Fcgamma complex is stable at pH values from 5.6 to pH 8.1. These data indicate that the mechanistic details of Fc binding by HCMV gp68 differ from those of host FcgammaRs and from that of HSV-1 gE-gI, suggesting distinct functional and recognition properties.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Sprague
authors.forename: Henrike
authors.initials: H
authors.lastname: Reinhard
authors.forename: Evelyn J
authors.initials: EJ
authors.lastname: Cheung
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Farley
authors.forename: Robin Deis
authors.initials: RD
authors.lastname: Trujillo
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
mesh_terms: D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D002850:Chromatography, Gel; D003587:Cytomegalovirus / Q000502:physiology*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D047468:Immunoprecipitation; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D020349:Surface Plasmon Resonance; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; C464820:UL119-UL118 glycoprotein, Human cytomegalovirus; D014764:Viral Proteins; C104832:gp34 protein, cytomegalovirus