Structure of the IgY-FcRY complex and its comparison with IgG-FcRn

Immunoglobulin Y (IgY), the avian counterpart to mammalian IgG and IgE, is transported across yolk sac membranes via the FcRY receptor, providing passive immunity to embryos. Although functionally analogous to the mammalian FcRn-IgG system, the molecular basis of IgY-FcRY interactions remains unclear. Here, we resolved the cryo-electron microscopy structure of the chicken IgY-FcRY complex at 3.06 Å resolution, revealing a distinctive binding interface. FcRY forms a double-ring architecture similar to other mannose receptor family members including PLA2R and DEC-205, yet its CTLD5 domain adopts a distinctive conformation to engage IgY-Fc. Mutational and functional assays validated critical interaction residues. Further analyses suggest that an inter-domain histidine network facilitates a pH-dependent conformational rearrangement of FcRY, enabling IgY binding and release. Together, these findings demonstrate the co-evolution of antibodies and receptors, and highlight the convergent evolution of a histidine-based pH-sensing mechanism in antibody transport.