Alteration of the Fc gamma RIIa dimer interface affects receptor signaling but not ligand binding.
The aggregation of cell surface FcRs by immune complexes induces a number of important Ab-dependent effector functions. However, despite numerous studies that examine receptor function, very little is known about the molecular organization of these receptors within the cell. In this study, protein complementation, mutagenesis, and ligand binding analyses demonstrate that human FcgammaRIIa is present as a noncovalent dimer form. Protein complementation studies found that FcgammaRIIa molecules are closely associated. Mutagenesis of the dimer interface, as identified by crystallographic analyses, did not affect ligand binding yet caused significant alteration to the magnitude and kinetics of receptor phosphorylation. The data suggest that the ligand binding and the dimer interface are distinct regions within the receptor, and noncovalent dimerization of FcgammaRIIa may be an essential feature of the FcgammaRIIa signaling cascade.
Powell
Maree S
MS
The Macfarlane Burnet Institute for Medical Research and Public Health Limited, Austin Health, Heidelberg, Victoria, Australia.
Barnes
Nadine C
NC
Bradford
Tessa M
TM
Musgrave
Ian F
IF
Wines
Bruce D
BD
Cambier
John C
JC
Hogarth
P Mark
PM
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D019281:Dimerization; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008024:Ligands; D008727:Methotrexate / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011392:Proline / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D012694:Serine / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D008024:Ligands; D010446:Peptide Fragments; D017452:Receptors, IgG; D012694:Serine; D011392:Proline; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate