6lxw
From Proteopedia
Cryo-EM structure of human secretory immunoglobulin A in complex with the N-terminal domain of SpsA
Structural highlights
Disease[IL2_HUMAN] Note=A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17. Function[IL2_HUMAN] Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells. [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 PubMedSecretory Immunoglobulin A (SIgA) is the most abundant antibody at the mucosal surface. It possesses two additional subunits besides IgA: the joining chain (J-chain) and secretory component (SC). SC is the ectodomain of the polymeric immunoglobulin receptor (pIgR), which functions to transport IgA to the mucosa. How the J-chain and pIgR/SC facilitate the assembly and secretion of SIgA remains incompletely understood. Furthermore, during the infection of Streptococcus pneumoniae, the pneumococcal adhesin SpsA hijacks pIgR/SC and SIgA to gain entry to human cells and evade host defense. How SpsA targets pIgR/SC and SIgA also remains elusive. Here we report a cryo-electron microscopy structure of the Fc region of IgA1 (Fcalpha) in complex with the J-chain and SC (Fcalpha-J-SC), which reveals the organization principle of SIgA. We also present a structure of Fcalpha-J-SC complexed with SpsA, which uncovers the specific interactions between SpsA and human pIgR/SC. These results advance the molecular understanding of SIgA and shed light on S. pneumoniae pathogenesis. Structural insights into secretory immunoglobulin A and its interaction with a pneumococcal adhesin.,Wang Y, Wang G, Li Y, Zhu Q, Shen H, Gao N, Xiao J Cell Res. 2020 May 12. pii: 10.1038/s41422-020-0336-3. doi:, 10.1038/s41422-020-0336-3. PMID:32398862[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Li, Y | Wang, G | Wang, Y | Xiao, J | Dimer | Immune system | Immunoglobulin | Secreted | Transcytosis
