The Major Birch Allergen, Bet v 1, Shows Affinity for a Broad Spectrum of Physiological Ligands

Mogensen, Jesper; Wimmer, Reinhard; Larsen, Jørgen Nedergaard; Spangfort, Michael D.; Otzen, Daniel E.

doi:10.1074/jbc.m202065200

Cited by 231 publications

(243 citation statements)

References 70 publications

(74 reference statements)

Supporting

Mentioning

220

Contrasting

Unclassified

Order By: Relevance

“…We interpret this phenomenon to indicate that daidzein does bind in the hydrophobic pocket but does not displace ANS. This phenomenon was observed with Bet v 1 and was thought to be due to increasing the quantum yield of the bound ANS (16). Fig.…”

Section: Figure 4 Superposition Of Ara H 8 (Shown In Brown) and Gly mentioning

confidence: 75%

See 1 more Smart Citation

Structure and Function of the Peanut Panallergen Ara h 8

Hurlburt

Offermann

McBride

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Figure 4 Superposition Of Ara H 8 (Shown In Brown) and Gly mentioning

confidence: 75%

“…Bet v 1 and its homologs from various species have been shown to bind small hydrophobic compounds. Mogensen et al (16) showed that flavonoids, cytokinins, and fatty acids bind to Bet v 1. PR-10c from birch is related to Bet v 1 and binds a variety of biologically important ligands (17).…”

mentioning

confidence: 99%

Structure and Function of the Peanut Panallergen Ara h 8

Hurlburt

Offermann

McBride

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…For calculation of binding stoichiometry, we determined the concentration of DHE from its absorbance at 328 nm and calculated its contribution toward absorbance at 280 nm using its reported extinction coefficients of 1.055 ϫ 10 4 and 1.686 ϫ 10 4 M Ϫ1 cm Ϫ1 at 328 and 280 nm, respectively (20,21). Control experiments adding DHE directly to methanol or to excess NPC2 in aqueous solution indicated that free DHE in organic solvent and DHE associated with NPC2 had similar extinction coefficients at 328 nm.…”

Section: Methodsmentioning

confidence: 99%

NPC2, the Protein Deficient in Niemann-Pick C2 Disease, Consists of Multiple Glycoforms That Bind a Variety of Sterols

Liou¹,

Dixit²,

Xu³

et al. 2006

Journal of Biological Chemistry

105

117

View full text Add to dashboard Cite

Niemann-Pick C disease is a fatal neurodegenerative disorder characterized by an endolysosomal accumulation of cholesterol and other lipids. One form of the disease is caused by a deficiency in NPC2, a soluble lysosomal glycoprotein that binds cholesterol. To better understand the biological function of NPC2 and how its deficiency results in disease, we have characterized the structural and functional properties of recombinant human protein. Highly purified NPC2 consists of a complex mixture of glycosylated isoforms, similar to that observed in human brain autopsy specimens. Mass spectrometric analysis revealed that of the three potential N-linked glycosylation sites present in the mature protein, Asn-19 is not utilized; Asn-39 is linked to an endoglycosidase H (Endo H)-sensitive oligosaccharide, and Asn-116 is variably utilized, either being unmodified or linked to Endo H-sensitive or Endo H-resistant oligosaccharides. All glycoforms are endocytosed and ameliorate the cholesterol storage phenotype of NPC2-deficient fibroblasts. In addition, the purified preparation contains a mixture of both free and lipid-bound protein. All glycoforms bind cholesterol, and sterol binding to NPC2 significantly alters its behavior upon cation-exchange chromatography. Based on this observation, we developed chromatography-based binding assays and determined that NPC2 forms an equimolar complex with the fluorescent cholesterol analog dehydroergosterol. In addition, we find that NPC2 binds a range of cholesterol-related molecules (cholesterol precursors, plant sterols, some oxysterols, cholesterol sulfate, cholesterol acetate, and 5-␣-cholestan-3-one) and that 27-hydroxysterol accumulates in NPC2-deficient mouse liver. Binding was not detected for various glycolipids, phospholipids, or fatty acids. These biochemical properties support a direct and specialized function of NPC2 in lysosomal sterol transport.

show abstract

“…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

110

106

View full text Add to dashboard Cite

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.

show abstract

The Major Birch Allergen, Bet v 1, Shows Affinity for a Broad Spectrum of Physiological Ligands

Cited by 231 publications

References 70 publications

Structure and Function of the Peanut Panallergen Ara h 8

Structure and Function of the Peanut Panallergen Ara h 8

NPC2, the Protein Deficient in Niemann-Pick C2 Disease, Consists of Multiple Glycoforms That Bind a Variety of Sterols

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

Contact Info

Product

Resources

About