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Crystal structure of the human leukocyte Fc receptor, FcγRIIa.

Nature Structural Biology volume 6, pages 437–442 (1999)Cite this article

Abstract

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 VLVH dimers, suggesting that two FcγRIIa molecules could cooperate to bind IgG in an asymmetric manner.

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Figure 1: Structural features of FcγRIIa and comparison with other leukocyte FcR and IgSF members.
Figure 2: Definition and structure of the IgG2 binding site from single residue mutations.
Figure 3: Molecular association at the crystallographic two–fold axis observed in the FcγRIIa crystals compared with interactions of VLVH19 and CD8α38.
Figure 4: Ig binding surface and interaction with IgG.

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Acknowledgements

We wish to thank A. van Donklaar for technical assistance and P.M. Colman, B.E. Loveland and H. Metzger for helpful discussions. We gratefully acknowledge help from C. Ogata, beamtime provided at X4A by the Howard Hughes Medical Institute, NSLS, support from the Australian Synchrotron Program and Brookhaven National Laboratory.

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Author notes

  1. Kelly F. Maxwell, Maree S. Powell and Peter A. Barton: These authors contributed equally.

Authors and Affiliations

  1. Biomolecular Research Institute, 343 Royal Parade, Parkville, 3052, Victoria, Australia

    Kelly F. Maxwell & Thomas P.J. Garrett

  2. Austin Research Institute, Austin and Repatriation Medical Centre, Studley Road, Heidelberg, 3084, Victoria, Australia

    Maree S. Powell, Mark D. Hulett, Ian F. C. McKenzie & P. Mark Hogarth

  3. School of Engineering and Science, Swinburne University of Technology, Victoria, 3122, Australia

    Peter A. Barton

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  1. Kelly F. Maxwell
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Correspondence to P. Mark Hogarth.

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Maxwell, K., Powell, M., Hulett, M. et al. Crystal structure of the human leukocyte Fc receptor, FcγRIIa. . Nat Struct Mol Biol 6, 437–442 (1999). https://doi.org/10.1038/8241

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