Mediation and Modulation of Antibody Function

Human Fcy receptors (FcyRs) for the Fc portion of IgG are major mediators of the adaptive immune response. Crystal structures of their extracellular domains were recently solved and shown to obey a common fold, resulting in a heart-shaped structure. Together with the multifunctional Fc fragment, whose structure was deciphered in the 1970s, the complex of an FcyR with Fc was recently crystallized. Its crystal structure indicates that despite the dimeric character of the Fc fragment, only one FcyR can bind to Fc, due to an introduced asymmetry within the homodimeric Fc, as well as by binding to symmetrically related residues of both Fc chains. Homology modelling suggested that the other FcyRs bind the Fc in a similar manner. The resolved complex structure can be regarded as a paradigm for Ig binding to Fc receptors and serves as a solid base for the design of compounds interfering with complex formation. Such molecules would be of invaluable benefit for the therapy of immunological disorders.