Crystal structure of the human leukocyte Fc receptor, FcγRIIa

Fcγ receptors bind IgG to initiate cellular responses against pathogens and soluble antigens. We have determined the three-dimensional structure of the extracellular portion of human FcγRIIa to 2.0 Å resolution providing a structural basis for the unique functions of the leukocyte FcR family. The receptor is composed of two immunoglobulin domains and arranged to expose the ligand-binding site at one end of domain 2. Using alanine mutants we find that the binding sites for IgG1 and 2 are similar but the relative importance of specific regions on the receptor varies. In crystals, FcγRIIa molecules associate to resemble V(L)V(H) dimers, suggesting that two FcγRIIa molecules could cooperate to bind IgG in an asymmetric manner.