3tsj | pdb_00003tsj

Crystal structure of Phl p 4, a grass pollen allergen with glucose dehydrogenase activity

spinqualitylabelsall models 3tsj, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3tsj is a 2 chain structure with sequence from Phleum pratense. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: FDA, NA, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q2I6V7_PHLPR Publication Abstract from PubMed BACKGROUND: Phl p 4 is a major pollen allergen but exhibits lower allergenicity than other major allergens. The natural protein is glycosylated and shows cross-reactivity with related and structurally unrelated allergens. OBJECTIVE: We sought to determine the high-resolution crystal structure of Phl p 4 and to evaluate the immunologic properties of the recombinant allergen in comparison with natural Phl p 4. METHODS: Different isoallergens of Phl p 4 were expressed, and the nonglycosylated mutant was crystallized. The specific role of protein and carbohydrate epitopes for allergenicity was studied by using IgE inhibition and basophil release assays. RESULTS: The 3-dimensional structure was determined by using x-ray crystallography at a resolution of 1.9 A. The allergen is a glucose dehydrogenase with a bicovalently attached flavin adenine dinucleotide. Glycosylated and nonglycosylated recombinant Phl p 4 showed identical inhibition of IgE binding, but compared with natural Phl p 4, all recombinant isoforms displayed a reduced IgE-binding inhibition. However, the recombinant protein exhibited an approximately 10-fold higher potency in basophil release assays than the natural protein. CONCLUSION: The crystal structure reveals the compact globular nature of the protein, and the observed binding pocket implies the size of the natural substrate. Plant-derived cross-reactive carbohydrate determinants (CCDs) appear to reduce the allergenicity of the natural allergen, whereas the Pichia pastoris-derived glycosylation does not. Our results imply yet undescribed mechanism of how CCDs dampen the immune response, leading to a novel understanding of the role of CCDs. Crystal structure and immunologic characterization of the major grass pollen allergen Phl p 4.,Zafred D, Nandy A, Pump L, Kahlert H, Keller W J Allergy Clin Immunol. 2013 Sep;132(3):696-703.e10. doi:, 10.1016/j.jaci.2013.03.021. Epub 2013 May 14. PMID:23683465 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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