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dc.creatorKaiser, Liselotte
dc.creatorĆirković-Veličković, Tanja
dc.creatorBadia-Martinez, Daniel
dc.creatorAdedoyin, Justus
dc.creatorThunberg, Sarah
dc.creatorHallen, Dan
dc.creatorBerndt, Kurt
dc.creatorGronlund, Hans
dc.creatorGafvelin, Guro
dc.creatorvan Hage, Marianne
dc.creatorAchour, Adnane
dc.date.accessioned2018-11-22T00:11:06Z
dc.date.available2018-11-22T00:11:06Z
dc.date.issued2007
dc.identifier.issn0022-2836
dc.identifier.urihttp://cherry.chem.bg.ac.rs/handle/123456789/848
dc.description.abstractFelis 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.en
dc.publisherAcademic Press Ltd- Elsevier Science Ltd, London
dc.rightsrestrictedAccess
dc.sourceJournal of Molecular Biology
dc.subjectcat allergenen
dc.subjectFel d 1en
dc.subjectcrystal structureen
dc.subjecttetrameren
dc.subjectcalciumen
dc.titleStructural characterization of the tetrameric form of the major cat allergen Fel d 1en
dc.typearticle
dc.rights.licenseARR
dcterms.abstractAцхоур, Aднане; ван Хаге, Марианне; Гафвелин, Гуро; Гронлунд, Ханс; Берндт, Курт; Ћирковић-Величковић, Тања; Тхунберг, Сарах; Aдедоyин, Јустус; Каисер, Лиселотте; Бадиа-Мартинез, Даниел; Халлен, Дан;
dc.citation.volume370
dc.citation.issue4
dc.citation.spage714
dc.citation.epage727
dc.identifier.wos000247904400009
dc.identifier.doi10.1016/j.jmb.2007.04.074
dc.citation.other370(4): 714-727
dc.citation.rankM21
dc.identifier.pmid17543334
dc.type.versionpublishedVersionen
dc.identifier.scopus2-s2.0-34249943865
dc.identifier.rcubKon_1801


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