Stabilization of the Dimeric Birch Pollen Allergen Bet v 1 Impacts Its Immunological Properties*

Background: Frequently reported dimerization of allergens may contribute to their allergenicity. Results: Polysulfide-bridged allergen dimers exhibit different allergenic properties compared with the monomer. Conclusion: The N-terminal region has a distinct susceptibility for modifications and impacts its protein-protein interaction characteristics. Significance: The crystal structures well mimic transient dimerization of the allergens in solution, providing a rational for effective IgE cross-linking on effector cells. 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.

• Publication year

  2013

• Venue

  Journal of Biological Chemistry

• Publication date

  2013-11-05

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.M113.518795PMID 24253036PMCID 3879576
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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