Crystal structure of the HSV-1 Fc receptor bound to Fc reveals a mechanism for antibody bipolar bridging

TitleCrystal structure of the HSV-1 Fc receptor bound to Fc reveals a mechanism for antibody bipolar bridging
Publication TypeJournal Article
Year of Publication2006
AuthorsSprague, E. R., Wang C., Baker D., & Bjorkman P. J.
JournalPLoS biology
Date Published2006 Jun
KeywordsAmino Acid Sequence, Binding Sites, Cell Membrane, Collaborative Publication, Computational Biology, Crystallography, X-Ray, Herpesvirus 1, Human, Humans, Hydrogen-Ion Concentration, Immunoglobulin Fc Fragments, Immunoglobulin G, Models, Molecular, Molecular Sequence Data, Mutagenesis, Insertional, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary, Receptors, IgG, Viral Proteins

Herpes simplex virus type-1 expresses a heterodimeric Fc receptor, gE-gI, on the surfaces of virions and infected cells that binds the Fc region of host immunoglobulin G and is implicated in the cell-to-cell spread of virus. gE-gI binds immunoglobulin G at the basic pH of the cell surface and releases it at the acidic pH of lysosomes, consistent with a role in facilitating the degradation of antiviral antibodies. Here we identify the C-terminal domain of the gE ectodomain (CgE) as the minimal Fc-binding domain and present a 1.78-angstroms CgE structure. A 5-angstroms gE-gI/Fc crystal structure, which was independently verified by a theoretical prediction method, reveals that CgE binds Fc at the C(H)2-C(H)3 interface, the binding site for several mammalian and bacterial Fc-binding proteins. The structure identifies interface histidines that may confer pH-dependent binding and regions of CgE implicated in cell-to-cell spread of virus. The ternary organization of the gE-gI/Fc complex is compatible with antibody bipolar bridging, which can interfere with the antiviral immune response.

Alternate JournalPLoS Biol.
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