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The History and Science of the Major Birch Pollen Allergen Bet v 1

Breiteneder, Heimo, Kraft, Dietrich·2023·Biomolecules
DOI 10.3390/biom13071151PMC PMC10377203
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Abstract

The term allergy was coined in 1906 by the Austrian scientist and pediatrician Clemens Freiherr von Pirquet. In 1976, Dietrich Kraft became the head of the Allergy and Immunology Research Group at the Department of General and Experimental Pathology of the University of Vienna. In 1983, Kraft proposed to replace natural extracts used in allergy diagnostic tests and vaccines with recombinant allergen molecules and persuaded Michael Breitenbach to contribute his expertise in molecular cloning as one of the mentors of this project. Thus, the foundation for the Vienna School of Molecular Allergology was laid. With the recruitment of Heimo Breiteneder as a young molecular biology researcher, the work began in earnest, resulting in the publication of the cloning of the first plant allergen Bet v 1 in 1989. Bet v 1 has become the subject of a very large number of basic scientific as well as clinical studies. Bet v 1 is also the founding member of the large Bet v 1-like superfamily of proteins with members—based on the ancient conserved Bet v 1 fold—being present in all three domains of life, i.e., archaea, bacteria and eukaryotes. This suggests that the Bet v 1 fold most likely already existed in the last universal common ancestor. The biological function of this protein was probably related to lipid binding. However, during evolution, a functional diversity within the Bet v 1-like superfamily was established. The superfamily comprises 25 families, one of which is the Bet v 1 family, which in turn is composed of 11 subfamilies. One of these, the PR-10-like subfamily of proteins, contains almost all of the Bet v 1 homologous allergens from pollen and plant foods. Structural and functional comparisons of Bet v 1 and its non-allergenic homologs of the superfamily will pave the way for a deeper understanding of the allergic sensitization process.

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Figure 1 Ribbon representations of birch pollen Bet v 1 (PDB 4A88) and homologs from beech pollen (Fag s 1; PDB 6ALK), apple (Mal d 1; PDB 5MMU), peanut (Ara h 8; PDB 4M9B), the hyperthermophilic archaeon Aeropyrum pernix (APE2225; 2NS9) and the extremely thermophilic bacterium Thermus thermophilus (TTHA0849; PDB 2D4R) rainbow-colored from blue at the N-terminus to red at the C-terminus. The 3D images were created with the molecular modeling system UCSF ChimeraX (https://www.rbvi.ucsf.edu/chimerax/, accessed on 9 June 2023).
Figure 1 Ribbon representations of birch pollen Bet v 1 (PDB 4A88) and homologs from beech pollen (Fag s 1; PDB 6ALK), apple (Mal d 1; PDB 5MMU), peanut (Ara h 8; PDB 4M9B), the hyperthermophilic archaeon Aeropyrum pernix (APE2225; 2NS9) and the extremely thermophilic bacterium Thermus thermophilus (TTHA0849; PDB 2D4R) rainbow-colored from blue at the N-terminus to red at the C-terminus. The 3D images were created with the molecular modeling system UCSF ChimeraX (https://www.rbvi.ucsf.edu/chimerax/, accessed on 9 June 2023).CC BY · PubMed Central
Figure 2 Ribbon representations of Bet v 1 (PDB 4A88) homologous structures from the yeast Saccharomyces cerevisiae. The StARkin domains of Lam2 (StARkin domain 1, PDB 5YQI; StARkin domain 2 as a swapped dimer, PDB 5YQQ) and of Lam4 (StARkin domain 1, PDB 5YQJ; StARkin domain 2, PDB 5YQP) are shown. The structures are rainbow-colored from blue at the N-terminus to red at the C-terminus. The 3D images were created with the molecular modeling system UCSF ChimeraX (https://www.rbvi.ucsf.edu/chimerax/, accessed on 19 June 2023).
Figure 2 Ribbon representations of Bet v 1 (PDB 4A88) homologous structures from the yeast Saccharomyces cerevisiae. The StARkin domains of Lam2 (StARkin domain 1, PDB 5YQI; StARkin domain 2 as a swapped dimer, PDB 5YQQ) and of Lam4 (StARkin domain 1, PDB 5YQJ; StARkin domain 2, PDB 5YQP) are shown. The structures are rainbow-colored from blue at the N-terminus to red at the C-terminus. The 3D images were created with the molecular modeling system UCSF ChimeraX (https://www.rbvi.ucsf.edu/chimerax/, accessed on 19 June 2023).CC BY · PubMed Central
Figure 3 Superposition of the ribbon structure of Bet v 1.0101 (PDB 4A88, aa2-160) in orange and the structure of the StARkin domain 1 of the yeast Lam4 protein (PDB 5YQJ, aa749-929). The 3D images were created with the molecular modeling system UCSF ChimeraX (https://www.rbvi.ucsf.edu/chimerax/, accessed on 19 June 2023).
Figure 3 Superposition of the ribbon structure of Bet v 1.0101 (PDB 4A88, aa2-160) in orange and the structure of the StARkin domain 1 of the yeast Lam4 protein (PDB 5YQJ, aa749-929). The 3D images were created with the molecular modeling system UCSF ChimeraX (https://www.rbvi.ucsf.edu/chimerax/, accessed on 19 June 2023).CC BY · PubMed Central

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Metadata

Authors
Breiteneder, H., & Kraft, D.
Venue
Biomolecules
Publisher
MDPI AG
Published
2023-07-19
Volume
13
Issue
7
Pages
1151
ISSN
2218-273X
DOI
10.3390/biom13071151
PMC
PMC10377203
Cited by
40
References
1
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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Breiteneder, H., & Kraft, D. (2023). The History and Science of the Major Birch Pollen Allergen Bet v 1. Biomolecules. https://doi.org/10.3390/biom13071151