6LX3

Cryo-EM structure of human secretory immunoglobulin A

Summary for 6LX3

• Entry DOI: 10.2210/pdb6lx3/pdb
• EMDB information: 30004
• Descriptor: Interleukin-2,Immunoglobulin heavy constant alpha 1, Immunoglobulin J chain, Polymeric immunoglobulin receptor (3 entities in total)
• Functional Keywords: immunoglobulin, dimer, transcytosis, secreted, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 208314.87

Authors

Wang, Y.,Wang, G.,Li, Y.,Xiao, J. (deposition date: 2020-02-10, release date: 2020-05-27, Last modification date: 2020-07-22)

Primary citation

Wang, Y.,Wang, G.,Li, Y.,Zhu, Q.,Shen, H.,Gao, N.,Xiao, J.
Structural insights into secretory immunoglobulin A and its interaction with a pneumococcal adhesin.
Cell Res., 30:602-609, 2020

PubMed Abstract: Secretory 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 (Fcα) in complex with the J-chain and SC (Fcα-J-SC), which reveals the organization principle of SIgA. We also present a structure of Fcα-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.

PubMed: 32398862
DOI: 10.1038/s41422-020-0336-3

Experimental method

ELECTRON MICROSCOPY (3.15 Å)