Alteration of the Fc[gamma]RIIa dimer interface affects receptor signaling but not ligand binding

Abstract

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 Fc[gamma]RIIa is present as a noncovalent dimer form. Protein complementation studies found that Fc[gamma]RIIa 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 Fc[gamma]RIIa may be an essential feature of the Fc[gamma]RIIa signaling cascade.