Proteopedia

8bpe

8:1 binding of FcMR on IgM pentameric core8:1 binding of FcMR on IgM pentameric core

Structural highlights

8bpe is a 19 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.63Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FCMR_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 PubMed

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. 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

  1. ↑ Kubagawa H, Oka S, Kubagawa Y, Torii I, Takayama E, Kang DW, Gartland GL, Bertoli LF, Mori H, Takatsu H, Kitamura T, Ohno H, Wang JY. Identity of the elusive IgM Fc receptor (FcmuR) in humans. J Exp Med. 2009 Nov 23;206(12):2779-93. PMID:19858324 doi:10.1084/jem.20091107
  2. ↑ Vire B, David A, Wiestner A. TOSO, the Fcmicro receptor, is highly expressed on chronic lymphocytic leukemia B cells, internalizes upon IgM binding, shuttles to the lysosome, and is downregulated in response to TLR activation. J Immunol. 2011 Oct 15;187(8):4040-50. PMID:21908732 doi:10.4049/jimmunol.1100532
  3. ↑ Murakami Y, Narayanan S, Su S, Childs R, Krzewski K, Borrego F, Weck J, Coligan JE. Toso, a functional IgM receptor, is regulated by IL-2 in T and NK cells. J Immunol. 2012 Jul 15;189(2):587-97. PMID:22675200 doi:10.4049/jimmunol.1200840
  4. ↑ Honjo K, Kubagawa Y, Kearney JF, Kubagawa H. Unique ligand-binding property of the human IgM Fc receptor. J Immunol. 2015 Feb 15;194(4):1975-82. PMID:25601920 doi:10.4049/jimmunol.1401866
  5. ↑ Lloyd KA, Wang J, Urban BC, Czajkowsky DM, Pleass RJ. Glycan-independent binding and internalization of human IgM to FCMR, its cognate cellular receptor. Sci Rep. 2017 Feb 23;7:42989. PMID:28230186 doi:10.1038/srep42989
  6. ↑ Meryk A, Pangrazzi L, Hagen M, Hatzmann F, Jenewein B, Jakic B, Hermann-Kleiter N, Baier G, Jylhävä J, Hurme M, Trieb K, Grubeck-Loebenstein B. Fcμ receptor as a Costimulatory Molecule for T Cells. Cell Rep. 2019 Mar 5;26(10):2681-2691.e5. PMID:30840890 doi:10.1016/j.celrep.2019.02.024
  7. ↑ Li Y, Shen H, Zhang R, Ji C, Wang Y, Su C, Xiao J. Immunoglobulin M perception by FcμR. Nature. 2023 Mar;615(7954):907-912. PMID:36949194 doi:10.1038/s41586-023-05835-w
  8. ↑ Chen Q, Menon RP, Masino L, Tolar P, Rosenthal PB. Structural basis for Fc receptor recognition of immunoglobulin M. Nat Struct Mol Biol. 2023 Jul;30(7):1033-1039. PMID:37095205 doi:10.1038/s41594-023-00985-x
  9. ↑ Chen Q, Menon RP, Masino L, Tolar P, Rosenthal PB. Structural basis for Fc receptor recognition of immunoglobulin M. Nat Struct Mol Biol. 2023 Jul;30(7):1033-1039. PMID:37095205 doi:10.1038/s41594-023-00985-x

8bpe, resolution 3.63Å

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