Work

Crystal Structure of the HSV-1 Fc Receptor Bound to Fc Reveals a Mechanism for Antibody Bipolar Bridging

Year: 2006

Type: article

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.

Source: PLoS Biology

DOI: 10.1371/journal.pbio.0040148

Authors: Elizabeth R Sprague, Chu Wang, David Baker, Pamela J Bjorkman

Institutions: California Institute of Technology, University of Washington, Howard Hughes Medical Institute

Language: English

Topic: Herpesvirus Infections and Treatments

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

Open Access status: gold

Estimated APC paid: $5,500

Funders: Leukemia and Lymphoma Society, California Institute of Technology, National Institutes of Health, National Institute of Allergy and Infectious Diseases