TY  - JOUR
AU  - Kaiser, Liselotte
AU  - Ćirković-Veličković, Tanja
AU  - Badia-Martinez, Daniel
AU  - Adedoyin, Justus
AU  - Thunberg, Sarah
AU  - Hallen, Dan
AU  - Berndt, Kurt
AU  - Gronlund, Hans
AU  - Gafvelin, Guro
AU  - van Hage, Marianne
AU  - Achour, Adnane
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/848
AB  - 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.
PB  - Academic Press Ltd- Elsevier Science Ltd, London
T2  - Journal of Molecular Biology
T1  - Structural characterization of the tetrameric form of the major cat allergen Fel d 1
VL  - 370
IS  - 4
SP  - 714
EP  - 727
DO  - 10.1016/j.jmb.2007.04.074
ER  - 

@article{
author = "Kaiser, Liselotte and Ćirković-Veličković, Tanja and Badia-Martinez, Daniel and Adedoyin, Justus and Thunberg, Sarah and Hallen, Dan and Berndt, Kurt and Gronlund, Hans and Gafvelin, Guro and van Hage, Marianne and Achour, Adnane",
year = "2007",
abstract = "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.",
publisher = "Academic Press Ltd- Elsevier Science Ltd, London",
journal = "Journal of Molecular Biology",
title = "Structural characterization of the tetrameric form of the major cat allergen Fel d 1",
volume = "370",
number = "4",
pages = "714-727",
doi = "10.1016/j.jmb.2007.04.074"
}

Kaiser, L., Ćirković-Veličković, T., Badia-Martinez, D., Adedoyin, J., Thunberg, S., Hallen, D., Berndt, K., Gronlund, H., Gafvelin, G., van Hage, M.,& Achour, A.. (2007). Structural characterization of the tetrameric form of the major cat allergen Fel d 1. in Journal of Molecular Biology
Academic Press Ltd- Elsevier Science Ltd, London., 370(4), 714-727.
https://doi.org/10.1016/j.jmb.2007.04.074

Kaiser L, Ćirković-Veličković T, Badia-Martinez D, Adedoyin J, Thunberg S, Hallen D, Berndt K, Gronlund H, Gafvelin G, van Hage M, Achour A. Structural characterization of the tetrameric form of the major cat allergen Fel d 1. in Journal of Molecular Biology. 2007;370(4):714-727.
doi:10.1016/j.jmb.2007.04.074 .

Kaiser, Liselotte, Ćirković-Veličković, Tanja, Badia-Martinez, Daniel, Adedoyin, Justus, Thunberg, Sarah, Hallen, Dan, Berndt, Kurt, Gronlund, Hans, Gafvelin, Guro, van Hage, Marianne, Achour, Adnane, "Structural characterization of the tetrameric form of the major cat allergen Fel d 1" in Journal of Molecular Biology, 370, no. 4 (2007):714-727,
https://doi.org/10.1016/j.jmb.2007.04.074 . .