Sprague, Elizabeth R. and Martin, W. Lance and Bjorkman, Pamela J. (2004) pH Dependence and Stoichiometry of Binding to the Fc Region of IgG by the Herpes Simplex Virus Fc Receptor gE-gI. Journal of Biological Chemistry, 279 (14). pp. 14184-14193. ISSN 0021-9258. http://resolver.caltech.edu/CaltechAUTHORS:SPRAjbc04
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Herpes simplex virus type 1 encodes two glycoproteins, gE and gI, that form a heterodimer on the surface of virions and infected cells. The gE-gI heterodimer has been implicated in cell-to-cell spread of virus and is a receptor for the Fc fragment of IgG. Previous studies localized the gE-gI-binding site on human IgG to a region near the interface between the CH2 and CH3 domains of Fc, which also serves as the binding site for bacterial and mammalian Fc receptors. Although there are two potential gE-gI-binding sites per Fc homodimer, only one gE-gI heterodimer binds per IgG in gel filtration experiments. Here we report production of recombinant human Fc molecules that contain zero, one, or two potential gE-gI-binding sites and use them in analytical ultracentrifugation experiments to show that two gE-gI heterodimers can bind to each Fc. Further characterization of the gE-gI interaction with Fc reveals a sharp pH dependence of binding, with KD values of ~340 and ~930 nM for the first and second binding events, respectively, at the slightly basic pH of the cell surface (pH 7.4), but undetectable binding at pH 6.0. This strongly pH-dependent interaction suggests a physiological role for gE-gI dissociation from IgG within acidic intracellular compartments, consistent with a mechanism whereby herpes simplex virus promotes intracellular degradation of anti-viral antibodies.
|Additional Information:||© 2004 the American Society for Biochemistry and Molecular Biology. Received for publication, December 5, 2003 , and in revised form, January 14, 2004. Originally published In Press as doi:10.1074/jbc.M313281200 on January 20, 2004. We thank Inder Nangiana, Cynthia Jones, and Peter Snow (Caltech Protein Expression Facility) for insect cell expression of gE-gI and gE; Noreen Tiangco for CHO cell expression of hdFc and nbFc; Anthony West, Anthony Giannetti, and Andrew Herr for advice on biosensor and analytical ultracentrifugation experiments; and Malini Raghavan and members of the Bjorkman laboratory for critical reading of the manuscript. This work was supported by a post-doctoral fellowship from the Leukemia and Lymphoma Society (to E.R.S.) and a Max Planck Research Award (to P.J.B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.|
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|Deposited On:||23 Dec 2006|
|Last Modified:||04 Nov 2016 19:19|
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