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

Journal Article · Wed Aug 08 04:00:00 EDT 2007 · PLOS Biol.4:e148,2006

OSTI ID:912575

Sprague, E R; Wang, C; Baker, D; Bjorkman, P J

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-{angstrom} CgE structure. A 5-{angstrom} gE-gI/Fc crystal structure, which was independently verified by a theoretical prediction method, reveals that CgE binds Fc at the C{sub H}2-C{sub 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.

• Research Organization: Stanford Linear Accelerator Center (SLAC)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC02-76SF00515
• OSTI ID: 912575
• Report Number(s): SLAC-REPRINT-2006-311
• Journal Information: PLOS Biol.4:e148,2006, Journal Name: PLOS Biol.4:e148,2006 Journal Issue: 6 Vol. 4
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
ANTIBODIES
CRYSTAL STRUCTURE
FORECASTING
HERPES SIMPLEX
IMMUNOGLOBULINS
LYSOSOMES
Other
OTHER
PROTEINS