6kxs | pdb_00006kxs
Cryo-EM structure of human IgM-Fc in complex with the J chain and the ectodomain of pIgR
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] [PIGR_HUMAN] This receptor binds polymeric IgA and IgM at the basolateral surface of epithelial cells. The complex is then transported across the cell to be secreted at the apical surface. During this process a cleavage occurs that separates the extracellular (known as the secretory component) from the transmembrane segment. [IGJ_HUMAN] Serves to link two monomer units of either IgM or IgA. In the case of IgM, the J chain-joined dimer is a nucleating unit for the IgM pentamer, and in the case of IgA it induces larger polymers. It also help to bind these immunoglobulins to secretory component.[UniProtKB:P01592] Publication Abstract from PubMedImmunoglobulin M (IgM) plays a pivotal role in both humoral and mucosal immunity. Its assembly and transport depend on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR), but the underlying molecular mechanisms of these processes are unclear. We report a cryo-electron microscopy structure of the Fc region of human IgM in complex with the J-chain and pIgR ectodomain. The IgM-Fc pentamer is formed asymmetrically, resembling a hexagon with a missing triangle. The tailpieces of IgM-Fc pack into an amyloid-like structure to stabilize the pentamer. The J-chain caps the tailpiece assembly and bridges the interaction between IgM-Fc and the polymeric immunoglobulin receptor, which undergoes a large conformational change to engage the IgM-J complex. These results provide a structural basis for the function of IgM. Structural insights into immunoglobulin M.,Li Y, Wang G, Li N, Wang Y, Zhu Q, Chu H, Wu W, Tan Y, Yu F, Su XD, Gao N, Xiao J Science. 2020 Feb 28;367(6481):1014-1017. doi: 10.1126/science.aaz5425. Epub 2020, Feb 6. PMID:32029689[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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