1h2o
From Proteopedia
(New page: 200px<br /><applet load="1h2o" size="450" color="white" frame="true" align="right" spinBox="true" caption="1h2o" /> '''SOLUTION STRUCTURE OF THE MAJOR CHERRY ALLER...) |
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| - | [[Image:1h2o.jpg|left|200px]]<br /><applet load="1h2o" size=" | + | [[Image:1h2o.jpg|left|200px]]<br /><applet load="1h2o" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1h2o" /> | caption="1h2o" /> | ||
'''SOLUTION STRUCTURE OF THE MAJOR CHERRY ALLERGEN PRU AV 1 MUTANT E45W'''<br /> | '''SOLUTION STRUCTURE OF THE MAJOR CHERRY ALLERGEN PRU AV 1 MUTANT E45W'''<br /> | ||
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| + | ==Overview== | ||
| + | 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 Glu45 to Trp45 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 Trp45, demonstrating that the side chain of Glu45 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 Lys44 to Glu. The almost complete loss of IgE reactivity to the Pru av 1 Pro112 mutant is due to disruption of its tertiary structure. Neither the mutation Ala112 nor deletion of the C-terminal residues 155-159 influenced IgE binding to Pru av 1. In conclusion, the structure of the P-loop partially explains the cross-reactivity pattern, and modulation of IgE-binding by site-directed mutagenesis is a promising approach to develop hypo-allergenic variants for patient-tailored specific immunotherapy. | ||
==About this Structure== | ==About this Structure== | ||
| - | 1H2O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Prunus_avium Prunus avium]. Full crystallographic information is available from [http:// | + | 1H2O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Prunus_avium Prunus avium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H2O OCA]. |
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| + | ==Reference== | ||
| + | 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 P, Lehmann K, Nerkamp J, Haase T, Wangorsch A, Fotisch K, Hoffmann S, Rosch P, Vieths S, Scheurer S, Biochem J. 2003 Nov 15;376(Pt 1):97-107. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12943529 12943529] | ||
[[Category: Prunus avium]] | [[Category: Prunus avium]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: structure]] | [[Category: structure]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:56:48 2008'' |
Revision as of 10:56, 21 February 2008
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SOLUTION STRUCTURE OF THE MAJOR CHERRY ALLERGEN PRU AV 1 MUTANT E45W
Overview
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 Glu45 to Trp45 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 Trp45, demonstrating that the side chain of Glu45 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 Lys44 to Glu. The almost complete loss of IgE reactivity to the Pru av 1 Pro112 mutant is due to disruption of its tertiary structure. Neither the mutation Ala112 nor deletion of the C-terminal residues 155-159 influenced IgE binding to Pru av 1. In conclusion, the structure of the P-loop partially explains the cross-reactivity pattern, and modulation of IgE-binding by site-directed mutagenesis is a promising approach to develop hypo-allergenic variants for patient-tailored specific immunotherapy.
About this Structure
1H2O is a Single protein structure of sequence from Prunus avium. Full crystallographic information is available from OCA.
Reference
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 P, Lehmann K, Nerkamp J, Haase T, Wangorsch A, Fotisch K, Hoffmann S, Rosch P, Vieths S, Scheurer S, Biochem J. 2003 Nov 15;376(Pt 1):97-107. PMID:12943529
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