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

Nature volume 406, pages 267–273 (2000)Cite this article

Abstract

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 Fcγ receptor (sFcγRIII, 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 Cγ2 domains and the hinge region. Upon complex formation the angle between the two sFcγRIII domains increases significantly and the Fc fragment opens asymmetrically. The high degree of amino acid conservation between sFCγRIII 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 FcγR–IgG complexes and the FcεRIα–IgE complex.

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Figure 1: The overall structure of the sFcγRIII–hFc1 complex.
Figure 2: Superposition of the complexed components with the free structures (Cα trace).
Figure 3: Structure based sequence alignment of the complex components.
Figure 4: The binding site.
Figure 5: Omit map of the hinge region.

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Acknowledgements

We thank R. E. Schmidt and T. Witte and the unknown myeloma patient for providing us with the monoclonal hIgG1, G. P. Bourenkov and H. D. Bartunik, MPG-ASMB DESY/Hamburg, for help with the diffraction measurements.

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Authors and Affiliations

  1. Max-Planck-Institut für Biochemie Abteilung Strukturforschung, Am Klopferspitz 18a, Martinsried, D-82152, Germany

    Peter Sondermann, Robert Huber, Vaughan Oosthuizen & Uwe Jacob

  2. Department of Biochemistry & Microbiology, University of Port Elizabeth, PO Box 1600, Port Elizabeth, 6000, South Africa

    Vaughan Oosthuizen

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  1. Peter Sondermann
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Correspondence to Peter Sondermann.

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Sondermann, P., Huber, R., Oosthuizen, V. et al. The 3.2-Å crystal structure of the human IgG1 Fc fragment–FcγRIII complex. Nature 406, 267–273 (2000). https://doi.org/10.1038/35018508

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