8SKV

Structure of human SIgA1 in complex with Streptococcus pyogenes protein M4 (Arp4)

8SKV の概要

• エントリーDOI: 10.2210/pdb8skv/pdb
• EMDBエントリー: 40568
• 分子名称: Immunoglobulin heavy constant alpha 1, Secretory component, Immunoglobulin J chain, ... (6 entities in total)
• 機能のキーワード: secretory immunoglobulin a, siga, iga, group a streptococcus, streptococcus pyogenes m protein, m4, arp4, infectious disease, protein complex, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 305408.38

構造登録者

Liu, Q.,Stadtmueller, B.M. (登録日: 2023-04-20, 公開日: 2023-10-25, 最終更新日: 2024-11-13)

主引用文献

Liu, Q.,Stadtmueller, B.M.
SIgA structures bound to Streptococcus pyogenes M4 and human CD89 provide insights into host-pathogen interactions.
Nat Commun, 14:6726-6726, 2023

PubMed Abstract: Immunoglobulin (Ig) A functions as monomeric IgA in the serum and Secretory (S) IgA in mucosal secretions. Host IgA Fc receptors (FcαRs), including human FcαR1/CD89, mediate IgA effector functions; however, human pathogen Streptococcus pyogenes has evolved surface-protein virulence factors, including M4, that also engage the CD89-binding site on IgA. Despite human mucosa serving as a reservoir for pathogens, SIgA interactions with CD89 and M4 remain poorly understood. Here we report cryo-EM structures of M4-SIgA and CD89-SIgA complexes, which unexpectedly reveal different SIgA-binding stoichiometry for M4 and CD89. Structural data, supporting experiments, and modeling indicate that copies of SIgA bound to S. pyogenes M4 will adopt similar orientations on the bacterium surface and leave one host FcαR binding site open. Results suggest unappreciated functional consequences associated with SIgA binding to host and bacterial FcαRs relevant to understanding host-microbe co-evolution, IgA effector functions and improving the outcomes of group A Streptococcus infection.

PubMed: 37872175
DOI: 10.1038/s41467-023-42469-y

実験手法

ELECTRON MICROSCOPY (3.1 Å)