Structural characterization of the tetrameric form of the major cat allergen Fel d 1
| Autor: | Adnane Achour, Hans Grönlund, Marianne van Hage, Dan Hallén, Tanja Cirkovic Velickovic, Justus Adédoyin, Kurt D. Berndt, Daniel Badia-Martinez, Guro Gafvelin, Sarah Thunberg, L. Kaiser |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Allergy crystal structure animal diseases Molecular Sequence Data Immunoglobulin E medicine.disease_cause Crystallography X-Ray cat allergen 03 medical and health sciences 0302 clinical medicine Allergen Tetramer Structural Biology Fel d 1 medicine Animals Uteroglobin Amino Acid Sequence Protein Structure Quaternary Molecular Biology Cells Cultured 030304 developmental biology Cell Proliferation Glycoproteins chemistry.chemical_classification 0303 health sciences calcium Binding Sites biology tetramer Allergens medicine.disease 030228 respiratory system chemistry Biochemistry biology.protein Felis domesticus Cats Calcium Cat allergen Glycoprotein Dimerization Hydrophobic and Hydrophilic Interactions Protein Binding |
| Zdroj: | Journal of Molecular Biology |
| ISSN: | 0022-2836 |
| Popis: | Felis domesticus allergen 1(Fel d 1) is a 35 kDa tetrameric glycoprotein formed by two heterodimers which elicits IgE responses in 95% of patients with allergy to cat. We have previously established in vitro conditions for the appropriate folding of recombinant Fel d 1 using a direct linkage of chain I to chain 2 (construct Fel d 1 (1 + 2)) and chain 2 to chain 1 (construct Fel d 1 (2 + 1)). Although the crystal structure of Fel d 1 (2 + 1) revealed a striking structural similarity to that of uteroglobin, a steroid-inducible cytokine-like molecule with anti-inflammatory and immunomodulatory properties, no functional tetrameric form of Fel d I could be identified. Here we present the crystal structure of the Fel d I (1 +2) tetramer at 1.6 angstrom resolution. Interestingly, the crystal structure of tetrameric Fel d I reveals two different calcium-binding sites. Symmetrically positioned on each side of the Fel d 1 tetramer, the external Ca2+ -binding sites correspond to a putative Ca2+- binding site previously suggested for uteroglobin. The second Ca2+-binding site lies within the dimerization interface, stabilizing the formation of the Fel d 1 tetramer, and inducing important local conformational changes that directly govern the shape of two water-filled cavities. The crystal structure suggests a potential portal for an unknown ligand. Alternatively, the two cavities could be used by the allergen as a conditional inner space allowing for the spatial rearrangement of centrally localized side-chains, such as Asp130, without altering the overall fold of the molecule. The striking structural similarity of the major cat allergen to uteroglobin, coupled to the identification in the present study of a common Ca2+ -binding site, let us speculate that Fel d I could provoke an allergic response through the modulation of phospholipase A2, by sequestering Ca ions in a similar manner as previously suggested for uteroglobin. (c) 2007 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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