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

PLoS Biol. 2006 Jun;4(6):e148. doi: 10.1371/journal.pbio.0040148. Epub 2006 May 2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Membrane / metabolism
  • Computational Biology
  • Crystallography, X-Ray
  • Herpesvirus 1, Human / immunology*
  • Humans
  • Hydrogen-Ion Concentration
  • Immunoglobulin Fc Fragments / chemistry*
  • Immunoglobulin Fc Fragments / metabolism
  • Immunoglobulin G / chemistry*
  • Immunoglobulin G / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Protein Binding / physiology
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • Receptors, IgG / chemistry*
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism

Substances

  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Receptors, IgG
  • Viral Proteins