Site-selectivity of Phl p 5 Modifications and their Influence on the Inflammatory Potential

  • Objective: Resolve how peroxynitrite and O3/NO2 reshape tyrosine chemistry in Phl p 5 and modulate TLR4 activation. Design: Recombinant Phl p 5 underwent defined ONOO−:Y titrations and O3/NO2 exposures. ND, HOY-D, and dityrosine cross-links were quantified; modified residues were assigned; TLR4 responses were benchmarked to native. Key results: Y285 exhibited highest susceptibility across pathways; Y236 remained unmodified. ND peaked at ONOO−:Y = 3:1 and at O3/NO2 = 10/200 ppb. The strongest hydroxylation arose with 200 ppb O3, predominating at Y112 and Y285. Cross-linking patterns diverged: ONOO− increased domain-1 connectivity while suppressing head/tail links; NO2 shifted cross-linking toward head/tail positions. Biological effect: ONOO− did not raise TLR4 activity, whereas 200 ppb O3 produced a ~6% increase. Conclusion: Phl p 5 modification is residue- and chemistry-specific. Ozone-driven hydroxylation correlates with higher TLR4 signaling, while peroxynitrite-drivenObjective: Resolve how peroxynitrite and O3/NO2 reshape tyrosine chemistry in Phl p 5 and modulate TLR4 activation. Design: Recombinant Phl p 5 underwent defined ONOO−:Y titrations and O3/NO2 exposures. ND, HOY-D, and dityrosine cross-links were quantified; modified residues were assigned; TLR4 responses were benchmarked to native. Key results: Y285 exhibited highest susceptibility across pathways; Y236 remained unmodified. ND peaked at ONOO−:Y = 3:1 and at O3/NO2 = 10/200 ppb. The strongest hydroxylation arose with 200 ppb O3, predominating at Y112 and Y285. Cross-linking patterns diverged: ONOO− increased domain-1 connectivity while suppressing head/tail links; NO2 shifted cross-linking toward head/tail positions. Biological effect: ONOO− did not raise TLR4 activity, whereas 200 ppb O3 produced a ~6% increase. Conclusion: Phl p 5 modification is residue- and chemistry-specific. Ozone-driven hydroxylation correlates with higher TLR4 signaling, while peroxynitrite-driven nitration/cross-linking leaves TLR4 unchanged. These relationships pinpoint reactive hotspots and suggest exposure-dependent mechanisms in pollutant-enhanced allergenicity.zeige mehrzeige weniger

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Metadaten
Autor*innen:Nadine Bothen
Koautor*innen:Anna Lena Leifke, Michael G. WellerORCiD, Ulrich PöschlORCiD, Janine FröhlichORCiD
Dokumenttyp:Posterpräsentation
Veröffentlichungsform:Präsentation
Sprache:Englisch
Jahr der Erstveröffentlichung:2025
Organisationseinheit der BAM:1 Analytische Chemie; Referenzmaterialien
1 Analytische Chemie; Referenzmaterialien / 1.5 Proteinanalytik
DDC-Klassifikation:Technik, Medizin, angewandte Wissenschaften / Ingenieurwissenschaften / Sanitär- und Kommunaltechnik; Umwelttechnik
Freie Schlagwörter:Allergen; Allergy; Grass pollen; Inflammation; Nitrogen oxides; Ozone; TLR4; Tyrosine modification
Themenfelder/Aktivitätsfelder der BAM:Umwelt
Umwelt / Umwelt-Material-Interaktionen
Veranstaltung:European Aerosol Conferences (EAC)
Veranstaltungsort:Lecce, Italy
Beginndatum der Veranstaltung:31.08.2025
Enddatum der Veranstaltung:05.09.2025
Zugehöriger Identifikator:https://eac2025.iasaerosol.it
Verfügbarkeit des Dokuments:Datei im Netzwerk der BAM verfügbar ("Closed Access")
Datum der Freischaltung:10.10.2025
Referierte Publikation:Nein
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