Abstract
Immunoglobulin-α (IgA)-bound antigens induce immune effector responses by activating the IgA-specific receptor FcαRI (CD89) on immune cells. Here we present crystal structures of human FcαRI alone and in a complex with the Fc region of IgA1 (Fcα). FcαRI has two immunoglobulin-like domains that are oriented at approximately right angles to each other. Fcα resembles the Fcs of immunoglobulins IgG and IgE, but has differently located interchain disulphide bonds and external rather than interdomain N-linked carbohydrates. Unlike 1:1 FcγRIII:IgG and FcɛRI:IgE complexes, two FcαRI molecules bind each Fcα dimer, one at each Cα2–Cα3 junction. The FcαRI-binding site on IgA1 overlaps the reported polymeric immunoglobulin receptor (pIgR)-binding site, which might explain why secretory IgA cannot initiate phagocytosis or bind to FcαRI-expressing cells in the absence of an integrin co-receptor.
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Acknowledgements
We thank E. R. Sprague for help with data collection; E. R. Sprague, L. M. Thomas, A. P. West and K. Locher for discussions; P. M. Snow and the Caltech Protein Expression Facility for FcαRI expression; C. L. White for initial FcαRI crystallization trials; staff of the Stanford Synchrotron Radiation Laboratory for technical support; and G. Waksman, M. J. Bennett, W. L. Martin and members of the Bjorkman laboratory for comments on the manuscript. This work was supported by funds from the Damon Runyon Cancer Research Foundation (to A.B.H.), the Howard Hughes Medical Institute (to P.J.B.) and the Ralph M. Parsons Foundation for computational support.
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41586_2003_BFnature01685_MOESM1_ESM.doc
Supplementary Tables: Table 1: Crystallographic statistics Table 2: RMS deviations between FcαRI or Fcα and related proteinsTable 3: Pairwise interactions in the FcαRI:Fcα interface (DOC 131 kb)
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Herr, A., Ballister, E. & Bjorkman, P. Insights into IgA-mediated immune responses from the crystal structures of human FcαRI and its complex with IgA1-Fc. Nature 423, 614–620 (2003). https://doi.org/10.1038/nature01685
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DOI: https://doi.org/10.1038/nature01685
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