The 3.2-Å crystal structure of the human IgG1 Fc fragment-FcγRIII complex

The immune response depends on the binding of opsonized antigens to cellular Fc receptors and the subsequent initiation of various cellular effector functions of the immune system. Here we describe the crystal structures of a soluble Fc gamma receptor (sFc gamma RIII, CD16), an Fc fragment from human IgG1 (hFc1) and their complex. In the 1:1 complex the receptor binds to the two halves of the Fc fragment in contact with residues of the C gamma 2 domains and the hinge region. Upon complex formation the angle between the two sFcgRIII domains increases significantly and the Fc fragment opens asymmetrically. The high degree of amino acid conservation between sFC gamma RIII and other Fc receptors, and similarly between hFc1 and related immunoglobulins, suggest similar structures and modes of association. Thus the described structure is a model for immune complex recognition and helps to explain the vastly differing affinities of other Fc gamma R-IgG complexes and the Fc epsilon RI alpha-IgE complex.