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Characterization of the 2:1 Complex between the Class I MHC-Related Fc Receptor and Its Fc Ligand in Solution

Martin, W. Lance and Bjorkman, Pamela J. (1999) Characterization of the 2:1 Complex between the Class I MHC-Related Fc Receptor and Its Fc Ligand in Solution. Biochemistry, 38 (39). pp. 12639-12647. ISSN 0006-2960. doi:10.1021/bi9913505.

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The neonatal Fc receptor (FcRn) facilitates the transfer of maternal immunoglobulin G (IgG) to offspring and prolongs the half-life of serum IgG. FcRn binds IgG in acidic intracellular vesicles and releases IgG upon exposure to the basic pH of the bloodstream. The crystal structure of an FcRn/Fc complex revealed FcRn dimers bridged by homodimeric Fc molecules to create an oligomeric array with two receptors per Fc [Burmeister et al. (1994) Nature 372, 379−383], consistent with the 2:1 FcRn:Fc stoichiometry observed in solution [Huber et al. (1993) J. Mol. Biol. 230, 1077−1083; Sánchez et al. (1999) Biochemistry 38, 9471−9476]. Two distinct 2:1 FcRn/Fc complexes were present in the cocrystal structure:  a complex containing an FcRn dimer interacting with an Fc and a complex in which single FcRn molecules are bound to both sides of the Fc homodimer. To determine which of the two possible 2:1 FcRn/Fc complexes exists in solution, we generated recombinant Fc molecules with zero, one, and two FcRn binding sites and studied their interactions with a soluble form of rat FcRn. The wild-type Fc with two FcRn binding sites binds two FcRn molecules under all assay conditions, and the nonbinding Fc with no FcRn binding sites shows no specific binding. The heterodimeric Fc with one FcRn binding site binds one FcRn molecule, suggesting that the 2:1 FcRn/wild-type Fc complex formed in solution consists of single FcRn molecules binding to both sides of Fc rather than an FcRn dimer binding to a single site on Fc.

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Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 1999 American Chemical Society. Received June 11, 1999; Revised Manuscript Received July 26, 1999. Publication Date (Web): September 3, 1999. Supported by a Camille and Henry Dreyfuss Teacher Scholar Award (P.J.B.), a grant from the NIH (AI/GM41239 to P.J.B.), and an NIH predoctoral training grant (5 T32 GM07616 to W.L.M.). We thank Gary Hathaway and the Caltech PPMAL for microchemical analyses, Anthony West and Luis Sánchez for helpful discussions, and members of the Bjorkman laboratory for critical reading of the manuscript.
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Camille and Henry Dreyfus FoundationUNSPECIFIED
NIH Predoctoral Fellowship5 T32 GM07616
Issue or Number:39
Record Number:CaltechAUTHORS:20170406-084759076
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Official Citation:Characterization of the 2:1 Complex between the Class I MHC-Related Fc Receptor and Its Fc Ligand in Solution W. Lance Martin and Pamela J. Bjorkman Biochemistry 1999 38 (39), 12639-12647 DOI: 10.1021/bi9913505
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75784
Deposited By: Tony Diaz
Deposited On:06 Apr 2017 15:56
Last Modified:15 Nov 2021 16:36

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