crystal structure of the hsv-1 fc receptor bound to fc reveals a mechanism for antibody bipolar bridging1型单纯疱疹病毒fc受体的晶体结构绑定到fc揭示了一种抗体双相衔接的机制.pdfVIP

PLoS BIOLOGY Crystal Structure of the HSV-1 Fc Receptor Bound to Fc Reveals a Mechanism for Antibody Bipolar Bridging 1 2 2,3 1,4* Elizabeth R. Sprague , Chu Wang , David Baker , Pamela J. Bjorkman 1 Division of Biology, California Institute of Technology, Pasadena, California, United States of America, 2 Department of Biochemistry, University of Washington, Seattle, Washington, United States of America, 3 Howard Hughes Medical Institute, University of Washington, Seattle, Washington, United States of America, 4 Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California United States of America 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-A CgE structure. A 5-A gE-gI/Fc crystal structure, which was independently verified by a theoretical prediction method, reveals that CgE binds Fc at the CH2-CH3 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.