Crystal structure of the human leukocyte Fc receptor, Fc gamma RIIa.

Fc gamma receptors bind IgG to initiate cellular responses against pathogen s and soluble antigens. We have determined the three-dimensional structure of the extracellular portion of human Fc gamma RIIa to 2.0 Angstrom resolut ion providing a structural basis for the unique functions of the leukocyte FcR family. The receptor is composed of two immunoglobulin domains and arra nged to expose the ligand-binding site at one end of domain 2. Using alanin e 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 crystal s, Fc gamma RIIa molecules associate to resemble VLVH dimers, suggesting th at two Fc gamma RIIa molecules could cooperate to bind IgG in an asymmetric manner.