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TitleStructure of the secretory immunoglobulin A core.
Journal, issue, pagesScience, Vol. 367, Issue 6481, Page 1008-1014, Year 2020
Publish dateFeb 28, 2020
AuthorsNikit Kumar / Christopher P Arthur / Claudio Ciferri / Marissa L Matsumoto /
PubMed AbstractSecretory 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 ...Secretory 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. However, 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 in which the JC templates IgA oligomerization and imparts asymmetry for pIgR binding and transcytosis. This framework will inform the design of future IgA-based therapeutics.
External linksScience / PubMed:32029686
MethodsEM (single particle)
Resolution2.9 - 3.0 Å
Structure data

20749

6ue7

EMDB-20749, PDB-6ue7:
Structure of dimeric sIgA complex
Method: EM (single particle) / Resolution: 2.9 Å

20750

6ue8

EMDB-20750, PDB-6ue8:
Structure of tetrameric sIgA complex (Class 1)
Method: EM (single particle) / Resolution: 3.0 Å

20751

6ue9

EMDB-20751, PDB-6ue9:
Structure of tetrameric sIgA complex (Class 2)
Method: EM (single particle) / Resolution: 2.9 Å

20752

6uea

EMDB-20752, PDB-6uea:
Structure of pentameric sIgA complex
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / immunoglobulin

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