Structural basis for Fc receptor recognition of immunoglobulin M

  • Nat Struct Mol Biol. 2023 Jul;30(7):1033-1039. doi: 10.1038/s41594-023-00985-x.
Qu Chen  1 ,  Rajesh P Menon  2 ,  Laura Masino  1 ,  Pavel Tolar  3  4 ,  Peter B Rosenthal  5
Affiliations
  • 1. Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK.
  • 2. Immune Receptor Activation Laboratory, The Francis Crick Institute, London, UK.
  • 3. Immune Receptor Activation Laboratory, The Francis Crick Institute, London, UK. [email protected].
  • 4. Institute of Immunity and Transplantation, University College London, London, UK. [email protected].
  • 5. Structural Biology of Cells and Viruses Laboratory, The Francis Crick Institute, London, UK. [email protected].
PMID: 37095205 DOI: 10.1038/s41594-023-00985-x
Abstract

Immunoglobulin Fc Receptors are cell surface transmembrane proteins that bind to the Fc constant region of antibodies and play critical roles in regulating immune responses by activation of immune cells, clearance of immune complexes and regulation of antibody production. FcμR is the immunoglobulin M (IgM) antibody isotype-specific Fc receptor involved in the survival and activation of B cells. Here we reveal eight binding sites for the human FcμR immunoglobulin domain on the IgM pentamer by cryogenic electron microscopy. One of the sites overlaps with the binding site for the polymeric immunoglobulin receptor (pIgR), but a different mode of FcμR binding explains its antibody isotype specificity. Variation in FcμR binding sites and their occupancy reflects the asymmetry of the IgM pentameric core and the versatility of FcμR binding. The complex explains engagement with polymeric serum IgM and the monomeric IgM B-cell receptor (BCR).