Investigation of the interaction between the class I MHC-related Fc receptor and its immunoglobulin G ligand.
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.
Raghavan
M
M
Division of Biology 156-29, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125.
Chen
M Y
MY
Gastinel
L N
LN
Bjorkman
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal; D001665:Binding Sites / Q000235:genetics; D005260:Female; D006183:H-2 Antigens / Q000737:chemistry / Q000378:metabolism*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013205:Staphylococcal Protein A / Q000737:chemistry / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG; D013205:Staphylococcal Protein A; D001613:beta 2-Microglobulin; D006639:Histidine