Crystal Structure of a Hypoallergenic Isoform of the Major Birch Pollen Allergen Bet v 1 and its Likely Biological Function as a Plant Steroid Carrier

Marković-Housley, Z.; Degano, Massimo; Lamba, Doriano; Roepenack‐Lahaye, Edda von; Clemens, Stephan; Susani, Markus; Ferreira, Fátima; Scheiner, Otto; Breiteneder, Heimo

doi:10.1016/s0022-2836(02)01197-x

Cited by 270 publications

(249 citation statements)

References 46 publications

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“…NMR spectroscopy, together with molecular modelling, fluorescence spectroscopy, X-ray crystallography and MS, provided strong evidence that the cavity of both Pru av 1 and Bet v 1 interacts with steroids and other lipids [7][8][9], but their exact physiological function remains unclear. The P-loop is one of three highly conserved regions on the surface of the Bet v 1 molecule proposed as IgE epitopes leading to cross-reactivity with pollen allergens of other trees of the Fagales order [5].…”

Section: Introductionmentioning

confidence: 99%

Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure

Neudecker

Lehmann

Nerkamp

et al. 2003

Biochemical Journal

109

106

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Birch pollinosis is often accompanied by adverse reactions to food due to pollen-allergen specific IgE cross-reacting with homologous food allergens. The tertiary structure of Pru av 1, the major cherry (Prunus avium) allergen, for example, is nearly identical with Bet v 1, the major birch (Betula verrucosa) pollen allergen. In order to define cross-reactive IgE epitopes, we generated and analysed mutants of Pru av 1 and Api g 1.0101, the major celery (Apium graveolens) allergen, by immunoblotting, EAST (enzyme allergosorbent test), CD and NMR spectroscopy. The mutation of Glu 45 to Trp 45 in the P-loop region, a known IgE epitope of Bet v 1, significantly reduced IgE binding to Pru av 1 in a subgroup of cherry-allergic patients. The backbone conformation of Pru av 1 wild-type is conserved in the three-dimensional structure of Pru av 1 Trp 45 , demonstrating that the side chain of Glu 45 is involved in a cross-reactive IgE epitope. Accordingly, for a subgroup of celery-allergic patients, IgE binding to the homologous celery allergen Api g 1.0101 was enhanced by the mutation of Lys 44 to Glu. The almost complete loss of IgE reactivity to the Pru av 1 Pro 112 mutant is due to disruption of its tertiary structure. Neither the mutation Ala 112 nor deletion of the Cterminal residues 155-159 influenced IgE binding to Pru av 1. In conclusion, the structure of the P-loop partially explains the crossreactivity pattern, and modulation of IgE-binding by site-directed mutagenesis is a promising approach to develop hypo-allergenic variants for patient-tailored specific immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure

Neudecker

Lehmann

Nerkamp

et al. 2003

Biochemical Journal

109

106

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“…This is revealed by the structures of a number of PR-10 proteins obtained by NMR and x-ray crystallography, such as Bet v 1 from birch (Betula spp. ; Gajhede et al, 1996;Markovic-Housley et al, 2003), four isoforms of LlPR10 from yellow lupin (Lupinus luteus; Biesiadka et al, 2002;Pasternak et al, 2005;Fernandes et al, 2008), VrCSBP (cytokininspecific binding protein) from mung bean (Vigna radiata; Pasternak et al, 2006), Pru av 1 from cherry (Prunus avium; Neudecker et al, 2001), and Ap g 1 from celery (Apium graveolens; Schirmer et al, 2005).…”

mentioning

confidence: 99%

The RNA Hydrolysis and the Cytokinin Binding Activities of PR-10 Proteins Are Differently Performed by Two Isoforms of the Pru p 1 Peach Major Allergen and Are Possibly Functionally Related

et al. 2009

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PR-10 proteins are a family of pathogenesis-related (PR) allergenic proteins playing multifunctional roles. The peach (Prunus persica) major allergen, Pru p 1.01, and its isoform, Pru p 1.06D, were found highly expressed in the fruit skin at the pit hardening stage, when fruits transiently lose their susceptibility to the fungal pathogen Monilinia spp. To investigate the possible role of the two Pru p 1 isoforms in plant defense, the recombinant proteins were expressed in Escherichia coli and purified. Light scattering experiments and circular dichroism spectroscopy showed that both proteins are monomers in solution with secondary structures typical of PR-10 proteins. Even though the proteins do not display direct antimicrobial activity, they both act as RNases, a function possibly related to defense. The RNase activity is different for the two proteins, and only that of Pru p 1.01 is affected in the presence of the cytokinin zeatin, suggesting a physiological correlation between Pru p 1.01 ligand binding and enzymatic activity. The binding of zeatin to Pru p 1.01 was evaluated using isothermal titration calorimetry, which provided information on the stoichiometry and on the thermodynamic parameters of the interaction. The structural architecture of Pru p 1.01 and Pru p 1.06D was obtained by homology modeling, and the differences in the binding pockets, possibly accounting for the observed difference in binding activity, were evaluated.

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“…The most rel evant termite-type allergens are the 7S and 11S globulins. 7S globulins include Arah1, Jugr2 and Sesi3, whereas the 11S globulins include the Arah3, soy glycinins, Bere2, Cora9 and Fage1 [32]. The third structure of the proteins belonging to the termite group consists of a series of antiparallel β leaves associated with an α-helix forming a cavity [32].…”

Section: Allergenic Vegetable Proteinsmentioning

confidence: 99%

“…7S globulins include Arah1, Jugr2 and Sesi3, whereas the 11S globulins include the Arah3, soy glycinins, Bere2, Cora9 and Fage1 [32]. The third structure of the proteins belonging to the termite group consists of a series of antiparallel β leaves associated with an α-helix forming a cavity [32]. This structure is also found in several lipocalin-like proteins involved in the transport of hydrophobic ligands, including milk β-lactoglobulin [32].…”

Section: Allergenic Vegetable Proteinsmentioning

confidence: 99%

“…The third structure of the proteins belonging to the termite group consists of a series of antiparallel β leaves associated with an α-helix forming a cavity [32]. This structure is also found in several lipocalin-like proteins involved in the transport of hydrophobic ligands, including milk β-lactoglobulin [32]. Further, plant prophylines share about 70% of the amino acid sequence homology [32][33][34].…”

Section: Allergenic Vegetable Proteinsmentioning

confidence: 99%

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Vegetable Proteins: Non-sensitizing Encapsulation Agents for Bioactive Compounds

Quiroz¹,

Durán²,

Ciro-Gómez³

et al. 2017

Allergen

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Plant-derived proteins are remarkable macromolecules of scientific interest because they represent an alternative to the animal-derived proteins and petroleum-derived polymers. Many food proteins especially those derived from animal sources could act as antigens in humans. For instance, milk proteins extracted from cows may cause food intolerance during infancy. Further, soybean, peanuts, tree nuts, fish, crustacean shellfish and egg proteins may act as antigens in 90% of children. Since the GI tract is permeable to intact antigens the oral intake of these proteins may generate gastrointestinal (50-80%), cutane ous (20-40%) and respiratory symptoms (4-25%). Most of these allergens are water-soluble glycoproteins that are resistant to acids and enzymes. Usually, these proteins have a small molecular weight (10,000-60,000 kDa), water solubility, glycosylation residues, and a rela tive resistance to heat and digestion. Allergenicity is less frequent in vegetable proteins due to their less flexible and non-compact structure. Allergenicity is also related to the resistance to proteolysis, post-translational glycosylation, presence of epitopes, and enzy matic proteolysis. Moreover, proteins serve as a coating material if structural modifica tions in the protein, either by physical, chemical or enzymatic mechanisms are conducted. As a result, their allergenicity is reduced, and their functional properties are enhanced.

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Crystal Structure of a Hypoallergenic Isoform of the Major Birch Pollen Allergen Bet v 1 and its Likely Biological Function as a Plant Steroid Carrier

Cited by 270 publications

References 46 publications

Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure

Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure

The RNA Hydrolysis and the Cytokinin Binding Activities of PR-10 Proteins Are Differently Performed by Two Isoforms of the Pru p 1 Peach Major Allergen and Are Possibly Functionally Related

Vegetable Proteins: Non-sensitizing Encapsulation Agents for Bioactive Compounds

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