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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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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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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DOI: https://doi.org/10.1038/8241
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