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

Sprague, Elizabeth R. and Wang, Chu and Baker, David and Bjorkman, Pamela J. (2006) Crystal Structure of the HSV-1 Fc Receptor Bound to Fc Reveals a Mechanism for Antibody Bipolar Bridging. PLoS Biology, 4 (6). Art. No. e148. ISSN 1544-9173. PMCID PMC1450327. https://resolver.caltech.edu/CaltechAUTHORS:SPRpbio06

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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-Å CgE structure. A 5-Å 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. The ternary organization of the gE-gI/Fc complex is compatible with antibody bipolar bridging, which can interfere with the antiviral immune response.


Item Type:Article
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1450327/PubMed CentralArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2006 Sprague et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: January 9, 2006; Accepted: March 7, 2006; Published: May 2, 2006 We thank Inder Nangiana, Peter Snow, and Bjoern Phillips (California Institute of Technology Protein Expression Facility) for insect cell expression of gE-gI and CgE; Evelyn Cheung and Liz Leyton for assistance in crystallization; Leonard Thomas for assistance with derivative screening; and Andrew Herr, Malini Raghavan, Elaine Bearer, and Anthony West for critical reading of the manuscript. N-terminal sequencing and mass spectrometry were done by the Protein/Peptide Microanalytical Lab at the California Institute of Technology. Crystallographic data were collected at Stanford Synchrotron Radiation Laboratory beamlines 9–1 and 9–2 with technical assistance from the staff. The Research Collaboratory for Structural Bioinformatics Protein Data Bank accession numbers (http://www.rcsb.org/pdb) are 2GIY for the CgE structure and 2GJ7 for the gE-gI/Fc complex structure. Competing interests. The authors have declared that no competing interests exist. Author contributions. ERS and PJB conceived and designed the experiments. ERS and CW performed the experiments. CW and DB contributed reagents/materials/analysis tools. ERS, CW, DB, and PJB analyzed the data and wrote the paper. Funding. This work was supported by funds from a Max Planck Research Award (PJB), a grant from the National Institutes of Health (2 R37 AI041239-06A1 to PJB), and a postdoctoral fellowship from the Leukemia and Lymphoma Society (ERS). Academic Editor: Skip Virgin, Washington University School of Medicine, United States of America
Funders:
Funding AgencyGrant Number
Max Planck SocietyUNSPECIFIED
NIH2 R37 AI041239-06A1
Leukemia and Lymphoma SocietyUNSPECIFIED
Issue or Number:6
PubMed Central ID:PMC1450327
Record Number:CaltechAUTHORS:SPRpbio06
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:SPRpbio06
Alternative URL:http://dx.doi.org/10.1371/journal.pbio.0040148
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2837
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:03 May 2006
Last Modified:02 Oct 2019 22:57

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