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

Powell MS, Barnes NC, Bradford TM, Musgrave IF, Wines BD, Cambier JC, Hogarth PM

  • Journal Journal of immunology (Baltimore, Md. : 1950)

  • Published 13 Jul 2006

  • Volume 176

  • ISSUE 12

  • Pagination 7489-94

  • DOI 10.4049/jimmunol.176.12.7489


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.