Structure of the secretory immunoglobulin A core.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
28 02 2020
28 02 2020
Historique:
received:
20
09
2019
accepted:
24
01
2020
pubmed:
8
2
2020
medline:
6
5
2020
entrez:
8
2
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32029686
pii: science.aaz5807
doi: 10.1126/science.aaz5807
doi:
Substances chimiques
Immunoglobulin A, Secretory
0
Immunoglobulin Fc Fragments
0
Immunoglobulin J-Chains
0
Receptors, Polymeric Immunoglobulin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1008-1014Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.