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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:p>Immunoglobulin E (IgE) drives allergic responses. The IgE-Fc (Fc\u03b5) receptor Fc\u03b5RI plays a critical role in transducing IgE signaling; nevertheless, certain IgG-Fc (Fc\u03b3) receptor (Fc\u03b3R) can also bind IgE in murine models. Here, we characterize Fc\u03b3R interactions with IgE and IgG in mice and rats, and report cryoelectron microscopy structures of rat Fc\u03b3RIV\u2013Fc\u03b5, mouse Fc\u03b3RIV\u2013Fc\u03b32b, and rat Fc\u03b3RIIB\u2013Fc\u03b5 complexes. Together with biochemical analyses, we reveal N-linked glycans as critical determinants of affinity and isotype specificity. Specifically, rat Fc\u03b3RIV exhibits preferential binding to IgE over IgG, while mouse Fc\u03b3RIV shows the opposite preference. A unique glycan\u2013glycan interaction involving Asn179 in rat Fc\u03b3RIV underlies its high-affinity IgE binding, whereas the absence of this glycosylation site in rat Fc\u03b3RIIB results in attenuated IgE recognition. In contrast, only hypoglycosylated mouse Fc\u03b3RIV at the equivalent position engages strongly with fucosylated IgG2b. Together, these results provide insights into species-specific IgE- and IgG-mediated immune responses.<\/jats:p>","DOI":"10.1073\/pnas.2609841123","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:37:27Z","timestamp":1789580247000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Glycans influence IgE and IgG recognition by rodent IgG-Fc receptors"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5432-973X","authenticated-orcid":false,"given":"Shirui","family":"Xu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02v51f717","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Peking University","place":["Beijing, People\u2019s Republic of 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