Researchers have mapped the complex structures of secretory immunoglobulin A (sIgA) in interaction with human CD89 and Streptococcus pyogenes M4, offering new insights into how our first line of mucosal defense operates. The study reveals the intricate ways these components may influence each other, impacting both bacterial survival strategies and host immune responses.
By Neha MathurSep 10 2023Reviewed by Benedette Cuffari, M.Sc. In a recent study posted to the bioRxiv* preprint server, researchers determined the cryogenic-electron microscopic structures of secretory immunoglobulin A -M4 and sigA-CD89 complexes.
Background Ig A is an antibody present in monomeric and secretory forms in serum and mucosal secretions of mammals, respectively. Both m and S forms of IgA contain fragment antigen-binding and Fc regions. Previous studies have shown that GAS strains M4 and M22 use a 29-amino acid-long residue to bind IgA; however, how these proteins interact with host ligands remains unknown. Even though most published studies have focused on mIgA, one study revealed an overlapping interface of M4 and CD89, which raises the possibility that M4 interferes with IgA effector functions.
Alphafold2-multimer was used to model the full-length M4 and align this protein to the M4-sIgA structure to create schematic representations of the complex on a bacterium surface. Mutational analysis and surface plasmon resonance binding assays were also used to investigate the contribution of each M4 residue on sIgA binding.
Both mIgA and sIgA bound two CD89 copies in vitro; however, the orientation and spacing of bound CD89 differed in CD89-mIgA and CD89-sIgA cryo-EM structures. Previous studies modeled that two copies of CD89 in sIgA were 99Å apart; however, the researchers of the current study observed this distance to be 108Å, thus indicating the need for additional studies to evaluate the host's CD89 function.