Abstract
The neonatal Fc receptor (FcRn) is structurally similar to class I major histocompatibility molecules. FcRn transports maternal immunoglobulin G (IgG) from ingested milk into the blood. IgG is bound at the pH of milk (pH 6.0-6.5) in the gut and released at the pH of blood (pH 7.5). We find that alteration of a histidine pair within the alpha 3 domain of FcRn and of a nearby loop (the FcRn counterpart of the class I CD8-binding loop) affects the affinity for IgG. Inhibition studies suggest the involvement of the FcRn B2-microglobulin domain in IgG binding. Fragment B of protein A inhibits FcRn binding to IgG, localizing the binding site on Fc for FcRn to the CH2-CH3 domain interface. Three histidines present at the CH2-CH3 domain interface of Fc could be partially responsible for the pH-dependent interaction between FcRn and IgG.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Animals, Newborn
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Antibodies, Monoclonal
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Binding Sites / genetics
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Female
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H-2 Antigens / chemistry
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H-2 Antigens / metabolism*
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Histidine / chemistry
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Humans
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Hydrogen-Ion Concentration
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Immunoglobulin G / chemistry
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Immunoglobulin G / metabolism*
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Mice
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Mice, Inbred BALB C
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Models, Molecular
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Molecular Sequence Data
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Molecular Structure
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Mutagenesis, Site-Directed
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Protein Conformation
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Receptors, IgG / chemistry
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Receptors, IgG / genetics
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Receptors, IgG / metabolism*
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Staphylococcal Protein A / chemistry
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Staphylococcal Protein A / metabolism
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beta 2-Microglobulin / immunology
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beta 2-Microglobulin / metabolism
Substances
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Antibodies, Monoclonal
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H-2 Antigens
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H-2Kb protein, mouse
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Immunoglobulin G
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Receptors, IgG
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Staphylococcal Protein A
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beta 2-Microglobulin
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Histidine