A native IgE in complex with profilin provides insights into allergen recognition and cross-reactivity

García-Ramírez, Benjamín; Mares-Mejía, Israel; Rodríguez-Hernández, Annia; Cano-Sánchez, Patricia; Torres-Larios, Alfredo; Ortega, Enrique; Rodríguez-Romero, Adela

doi:10.1038/s42003-022-03718-w

Title: A native IgE in complex with profilin provides insights into allergen recognition and cross-reactivity

Journal Article · 27 July 2022 · Communications Biology

DOI: https://doi.org/10.1038/s42003-022-03718-w · OSTI ID:1982175

^[1];

^[1]; Rodríguez-Hernández, Annia ^[1]; Cano-Sánchez, Patricia ^[1];

^[1]; Ortega, Enrique ^[1];

^[1]

Univ. Nacional Autonoma de Mexico (UNAM), Mexico City (Mexico)

Allergies have become a rising health problem, where plentiful substances can trigger IgE-mediated allergies in humans. While profilins are considered minor allergens, these ubiquitous proteins are primary molecules involved in cross-reactivity and pollen-food allergy syndrome. Here we report the first crystal structures of murine Fab/IgE, with its chains naturally paired, in complex with the allergen profilin from Hevea brasiliensis (Hev b 8). The crystallographic models revealed that the IgE’s six complementarity-determining regions (CDRs) interact with the allergen, comprising a rigid paratope-epitope surface of 926 Å², which includes an extensive network of interactions. Interestingly, we also observed previously unreported flexibility at Fab/IgE’s elbow angle, which did not influence the shape of the paratope. The Fab/IgE exhibits a high affinity for Hev b 8, even when using 1 M NaCl in BLI experiments. Finally, based on the encouraging cross-reactivity assays using two mutants of the maize profilin (Zea m 12), this antibody could be a promising tool in IgE engineering for diagnosis and research applications.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)

Sponsoring Organization:: Conacyt, Mexico City; National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER); Universidad Nacional Autónoma de México (UNAM) (DGAPA)

Grant/Contract Number:: SC0012704

OSTI ID:: 1982175

Journal Information:: Communications Biology, Journal Name: Communications Biology Journal Issue: 1 Vol. 5; ISSN 2399-3642

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

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Title: A native IgE in complex with profilin provides insights into allergen recognition and cross-reactivity

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