6ue8 | pdb_00006ue8
Structure of tetrameric sIgA complex (Class 1)
Structural highlights
Function[IGHA2_HUMAN] Ig alpha is the major immunoglobulin class in body secretions. It may serve both to defend against local infection and to prevent access of foreign antigens to the general immunologic system. [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] [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. Publication Abstract from PubMedSecretory immunoglobulin A (sIgA) represents the immune system's first-line of defense against mucosal pathogens. IgAs are transported across the epithelium, as dimers and higher-order polymers, by the polymeric immunoglobulin receptor (pIgR). Upon reaching the luminal side, sIgAs mediate host protection and pathogen neutralization. In recent years, an increasing amount of attention has been given to IgA as a novel therapeutic antibody. Despite extensive studies sIgA structures have remained elusive. Here, we determine the atomic-resolution structures of dimeric, tetrameric, and pentameric IgA-Fc linked by the joining chain (JC) and in complex with the secretory component of the pIgR. We suggest a mechanism where the JC templates IgA oligomerization and imparts asymmetry for pIgR binding and transcytosis. This framework will inform the design of future IgA-based therapeutics. Structure of the secretory immunoglobulin A core.,Kumar N, Arthur CP, Ciferri C, Matsumoto ML Science. 2020 Feb 6. pii: science.aaz5807. doi: 10.1126/science.aaz5807. PMID:32029686[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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