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
Volume4
Issue6
Paginatione148
Date Published2006 Jun
ISSN1545-7885
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
Abstract

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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