Structural highlights
Disease
IGHM_HUMAN Autosomal agammaglobulinemia. The disease is caused by mutations affecting the gene represented in this entry.[1]
Function
IGHM_HUMAN IgM antibodies play an important role in primary defense mechanisms. They have been shown to be involved in early recognition of external invaders like bacteria and viruses, cellular waste and modified self, as well as in recognition and elimination of precancerous and cancerous lesions. The membrane-bound form is found in the majority of normal B-cells alongside with IgD. Membrane-bound IgM induces the phosphorylation of CD79A and CD79B by the Src family of protein tyrosine kinases. It may cause death of cells by apoptosis. It is also found in soluble form, which represents about 30% of the total serum immunoglobulins where it is found almost exclusively as a homopentamer. After the antigen binds to the B-cell receptor, the secreted form is secreted in large amounts.[2]
Publication Abstract from PubMed
Placental malaria is caused by Plasmodium falciparum-infected erythrocytes (IEs) adhering to chondroitin sulfate proteoglycans in placenta via VAR2CSA-type PfEMP1. Human pentameric immunoglobulin M (IgM) binds to several types of PfEMP1, including VAR2CSA via its Fc domain. Here, a 3.6 A cryo-electron microscopy map of the IgM-VAR2CSA complex reveals that two molecules of VAR2CSA bind to the Cmicro4 of IgM through their DBL3X and DBL5epsilon domains. The clockwise and anti-clockwise rotation of the two VAR2CSA molecules on opposite faces of IgM juxtaposes C-termini of both VAR2CSA near the J chain, where IgM creates a wall between both VAR2CSA molecules and hinders its interaction with its receptor. To support this, we show when VAR2CSA is bound to IgM, its staining on IEs as well as binding of IEs to chondroitin sulfate A in vitro is severely compromised.
Cryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding of Plasmodium falciparum to Chondroitin Sulfate A.,Akhouri RR, Goel S, Skoglund U Nat Commun. 2023 Oct 12;14(1):6391. doi: 10.1038/s41467-023-41838-x. PMID:37828011[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trubel H, Pachman LM, Kitchingman GR, Campana D, Rohrer J, Conley ME. Mutations in the mu heavy-chain gene in patients with agammaglobulinemia. N Engl J Med. 1996 Nov 14;335(20):1486-93. PMID:8890099 doi:http://dx.doi.org/10.1056/NEJM199611143352003
- ↑ Tisch R, Roifman CM, Hozumi N. Functional differences between immunoglobulins M and D expressed on the surface of an immature B-cell line. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6914-8. PMID:3137579
- ↑ Akhouri RR, Goel S, Skoglund U. Cryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding of Plasmodium falciparum to Chondroitin Sulfate A. Nat Commun. 2023 Oct 12;14(1):6391. PMID:37828011 doi:10.1038/s41467-023-41838-x
