title: Stabilization of the dimeric birch pollen allergen Bet v 1 impacts its immunological properties.
abstract: Many allergens share several biophysical characteristics, including the capability to undergo oligomerization. The dimerization mechanism in Bet v 1 and its allergenic properties are so far poorly understood. Here, we report crystal structures of dimeric Bet v 1, revealing a noncanonical incorporation of cysteine at position 5 instead of genetically encoded tyrosine. Cysteine polysulfide bridging stabilized different dimeric assemblies, depending on the polysulfide linker length. These dimers represent quaternary arrangements that are frequently observed in related proteins, reflecting their prevalence in unmodified Bet v 1. These conclusions were corroborated by characteristic immunologic properties of monomeric and dimeric allergen variants. Hereby, residue 5 could be identified as an allergenic hot spot in Bet v 1. The presented results refine fundamental principles in protein chemistry and emphasize the importance of protein modifications in understanding the molecular basis of allergenicity.
authors.affiliation: From the Structural Biology Group, Department of Molecular Biology.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kofler
authors.forename: Chloé
authors.initials: C
authors.lastname: Ackaert
authors.forename: Martin
authors.initials: M
authors.lastname: Samonig
authors.forename: Claudia
authors.initials: C
authors.lastname: Asam
authors.forename: Peter
authors.initials: P
authors.lastname: Briza
authors.forename: Jutta
authors.initials: J
authors.lastname: Horejs-Hoeck
authors.forename: Chiara
authors.initials: C
authors.lastname: Cabrele
authors.forename: Fatima
authors.initials: F
authors.lastname: Ferreira
authors.forename: Albert
authors.initials: A
authors.lastname: Duschl
authors.forename: Christian
authors.initials: C
authors.lastname: Huber
authors.forename: Hans
authors.initials: H
authors.lastname: Brandstetter
mesh_terms: D052179:Antigens, Plant / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D029662:Betula / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship
chemical_list: D052179:Antigens, Plant; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula
keywords: Allergen; Crystal Structure; Dimerization; Mass Spectrometry (MS); Noncanonical Amino Acid Incorporation; Polysulfide Linking; Position-specific Alteration of Genetic Code; Post-translational Modification; Protein Assembly