8bpe
8:1 binding of FcMR on IgM pentameric core
Structural highlights
FunctionFCMR_HUMAN High-affinity Fc receptor for immunoglobulin M (IgM), both secreted and membrane-bound IgM (PubMed:19858324, PubMed:22675200, PubMed:36949194, PubMed:37095205). Primarily regulates IgM transport and homeostasis. In lymphoid cells, enables exocytosis of membrane-bound IgM on the plasma membrane as well as endocytosis of IgM-antigen complexes toward lysosomes for degradation. In mucosal epithelium, mediates retrotranscytosis of antigen-IgM complexes across mucosal M cells toward antigen-presenting cells in mucosal lymphoid tissues (PubMed:21908732, PubMed:28230186). Triggers costimulatory signaling and mediates most of IgM effector functions involved in B cell development and primary immune response to infection. Likely limits tonic IgM BCR signaling to self-antigens for proper negative selection of autoreactive B cells in the bone marrow and for the maintenance of regulatory B cell pool in peripheral lymphoid organs. Mediates antibody responses to T cell-dependent and T cell-independent antigens and promotes induction of an efficient neutralizing IgG response. Engages in cross-talk with antigen-receptor signaling via the non-canonical NF-kappa-B, MAP kinases and calcium signaling pathways (PubMed:19858324, PubMed:22675200, PubMed:25601920, PubMed:30840890).[1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedImmunoglobulin 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. FcmuR 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 FcmuR 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 FcmuR binding explains its antibody isotype specificity. Variation in FcmuR binding sites and their occupancy reflects the asymmetry of the IgM pentameric core and the versatility of FcmuR binding. The complex explains engagement with polymeric serum IgM and the monomeric IgM B-cell receptor (BCR). Structural basis for Fc receptor recognition of immunoglobulin M.,Chen Q, Menon RP, Masino L, Tolar P, Rosenthal PB Nat Struct Mol Biol. 2023 Jul;30(7):1033-1039. doi: 10.1038/s41594-023-00985-x. , Epub 2023 Apr 24. PMID:37095205[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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