Stabilization of the dimeric birch pollen allergen Bet v 1 impacts its immunological properties

Stefan Kofler, Chloé Ackaert, Martin Samonig, Claudia Asam, Peter Briza, Jutta Horejs-Hoeck, Chiara Cabrele, Fatima Ferreira, Albert Duschl, Christian Huber, Hans Brandstetter

    Research output: Contribution to journalArticle

    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.

    Original languageEnglish
    Pages (from-to)540-551
    Number of pages12
    JournalJournal of Biological Chemistry
    Volume289
    Issue number1
    DOIs
    Publication statusPublished - 3 Jan 2014

    Bibliographical note

    289(1)

    Fields of Science and Technology Classification 2012

    • 106 Biology
    • 302 Clinical Medicine

    Keywords

    • Antigens, Plant/chemistry
    • Betula/chemistry
    • Plant Proteins/chemistry
    • Protein Multimerization
    • Protein Stability
    • Protein Structure, Quaternary
    • Structure-Activity Relationship

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