Identification of the IgG binding site of the human low affinity receptor for IgG Fc gamma RII. Enhancement and ablation of binding by site-directed mutagenesis.
Fc receptor-antibody interactions are key mechanisms through which antibody effector functions are mediated. The low affinity receptor for IgG, Fc gamma RII, is expressed on most hematopoietic cells, and through the binding of immune complexes mediates a large spectrum of biological responses vital for resistance to infection and the regulation of immunity. In this study the key residues of human Fc gamma RII involved in the interaction with IgG1 have been identified. Chimeric receptors composed of extracellular regions of Fc gamma RII and the Fc epsilon RI alpha chain have been used to localize the IgG1 binding site of Fc gamma RII to an 8-residue stretch in the second extracellular domain, Asn154 to Ser161. Site-directed mutagenesis of this region revealed that substitution of Ile155 or Gly156 with alanine ablated the binding of human and mouse IgG1, whereas replacement of Leu159, Phe160, or Ser161 with alanine enhanced binding. Molecular modeling has been used to generate a putative 3-dimensional model structure of the second extracellular domain of Fc gamma RII, suggesting that the binding site lies in an exposed loop region at the interface of domains 1 and 2.
Hulett
M D
MD
Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia.
Witort
E
E
Brinkworth
R I
RI
McKenzie
I F
IF
Hogarth
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D011487:Protein Conformation; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D017452:Receptors, IgG