Structural evolution of Fcα/μR-mediated antibody recognition
- 1University of Illinois Urbana-Champaign
Abstract
The Fc alpha-mu receptor (Fc/R) is an ancient Fc-receptor sharing common ancestry with the polymeric Ig receptor (pIgR) and binding polymeric IgM and IgA ligands. In several vertebrate lineages, including birds, Fc/R may serve as the sole IgM and IgA Fc receptor; yet its evolution and ligand-recognition mechanisms across vertebrates remain poorly understood. Here, we identify FCAMR expression in duck (Anas platyrhynchos, ap) lymphoid tissues and demonstrate that recombinantly expressed apFc/R ectodomain binds apIgM and apIgA ligands. apFc/R affinity was ~10-fold higher for apIgM versus apIgA and ~10-fold higher than mouse (mm) Fc/R. Cryo-EM structures of apFc/R in complex with pentameric apIgM (3.27 [A]) and tetrameric apIgA (3.57 [A]) showed three Ig-like domains (D1-D3) bound asymmetrically with 1:1 stoichiometry. Comparisons to avian pIgR, which contains four Ig-like domains (D1-D4), revealed overlapping contacts between apFc/R-D1 and pIgR-D1. apFc/R D2-D3 engaged sites similar to pIgR D3-D4, yet formed distinct contact networks. Parallel analysis of a mmFc/R-mmIgM structure (4.13 [A]) revealed mmFc/R's single Ig-domain bound analogous to apFc/R-D1 and to mammalian pIgR-D1, whereas downstream ectodomain regions were not observed. Collectively, the data elucidate PIGR-family mechanisms across vertebrates, providing a foundation for delineating common and divergent functions.
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BibTeX
@misc{seal2026structural,
title = {{Structural evolution of Fcα/μR-mediated antibody recognition}},
author = {M. Seal and W. N. Harrington and E. M. Flaugher and R. J. Webby and B. M. Stadtmueller},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.764962},
url = {https://www.biorxiv.org/content/10.64898/2026.11.06.764962v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Structural evolution of Fcα/μR-mediated antibody recognition
AU - M. Seal
AU - W. N. Harrington
AU - E. M. Flaugher
AU - R. J. Webby
AU - B. M. Stadtmueller
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.64898/2026.11.06.764962
UR - https://www.biorxiv.org/content/10.64898/2026.11.06.764962v1
AB - The Fc alpha-mu receptor (Fc/R) is an ancient Fc-receptor sharing common ancestry with the polymeric Ig receptor (pIgR) and binding polymeric IgM and IgA ligands. In several vertebrate lineages, including birds, Fc/R may serve as the sole IgM and IgA Fc receptor; yet its evolution and ligand-recognition mechanisms across vertebrates remain poorly understood. Here, we identify FCAMR expression in duck (Anas platyrhynchos, ap) lymphoid tissues and demonstrate that recombinantly expressed apFc/R ectodomain binds apIgM and apIgA ligands. apFc/R affinity was ~10-fold higher for apIgM versus apIgA and ~10-fold higher than mouse (mm) Fc/R. Cryo-EM structures of apFc/R in complex with pentameric apIgM (3.27 [A]) and tetrameric apIgA (3.57 [A]) showed three Ig-like domains (D1-D3) bound asymmetrically with 1:1 stoichiometry. Comparisons to avian pIgR, which contains four Ig-like domains (D1-D4), revealed overlapping contacts between apFc/R-D1 and pIgR-D1. apFc/R D2-D3 engaged sites similar to pIgR D3-D4, yet formed distinct contact networks. Parallel analysis of a mmFc/R-mmIgM structure (4.13 [A]) revealed mmFc/R's single Ig-domain bound analogous to apFc/R-D1 and to mammalian pIgR-D1, whereas downstream ectodomain regions were not observed. Collectively, the data elucidate PIGR-family mechanisms across vertebrates, providing a foundation for delineating common and divergent functions.
ER -