1H2O

SOLUTION STRUCTURE OF THE MAJOR CHERRY ALLERGEN PRU AV 1 MUTANT E45W

Summary for 1H2O

• Entry DOI: 10.2210/pdb1h2o/pdb
• Related: 1B6F 1BTV 1BV1 1E09 1FSK 1QMR
• Descriptor: MAJOR ALLERGEN PRU AV 1 (1 entity in total)
• Functional Keywords: allergen, major cherry allergen, pathogenesis-related protein, heteronuclear nmr, plant defense
• Biological source: PRUNUS AVIUM (SWEET CHERRY)
• Total number of polymer chains: 1
• Total formula weight: 17610.78

Authors

Neudecker, P.,Lehmann, K.,Nerkamp, J.,Schweimer, K.,Sticht, H.,Boehm, M.,Scheurer, S.,Vieths, S.,Roesch, P. (deposition date: 2002-08-12, release date: 2003-08-28, Last modification date: 2024-05-15)

Primary citation

Neudecker, P.,Lehmann, K.,Nerkamp, J.,Haase, T.,Wangorsch, A.,Fotisch, K.,Hoffmann, S.,Roesch, P.,Vieths, S.,Scheurer, S.
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
Biochem.J., 376:97-, 2003

PubMed Abstract: 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.

PubMed: 12943529
DOI: 10.1042/BJ20031057

Experimental method

SOLUTION NMR