TY - JOUR
T1 - SIgA structures bound to Streptococcus pyogenes M4 and human CD89 provide insights into host-pathogen interactions
AU - Liu, Qianqiao
AU - Stadtmueller, Beth M.
N1 - This work was supported by NIH R01 AI165570 (PI Beth Stadtmueller), University of Illinois start-up funding and the Michael A. Recny Graduate Fellowship (awarded to Q.L.). Cryo-Electron microscopy data were collected at the Purdue Cryo-EM facility ( http://cryoem.bio.purdue.edu ) with assistance from Thomas Klose and the Stanford-SLAC Cryo-EM Center (SC) supported by the National Institutes of Health Common Fund Transformative High Resolution Cryo-Electron Microscopy program (U24 GM129541) with assistance from Htet A. Khant. We thank members of the Stadtmueller lab for insightful discussion and Sarah Leonard for supporting SPR experiments. 2 2
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-023-42469-y
DO - 10.1038/s41467-023-42469-y
M3 - Article
C2 - 37872175
AN - SCOPUS:85174688631
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 6726
ER -