Crystal Structure of the Dog Lipocalin Allergen Can f 2: Implications for Cross-reactivity to the Cat Allergen Fel d 4 |
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Authors: | Chaithanya Madhurantakam Ola B Nilsson Hannes Uchtenhagen Tiiu Saarne Tatyana Sandalova Adnane Achour |
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Institution: | 1 Centre for Infectious Medicine, F59, Department of Medicine Huddinge, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden 2 Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden 3 Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden 4 Phadia AB, Uppsala, Sweden 5 Department of Medical Biophysics and Biochemistry, Karolinska Institutet, Stockholm, Sweden 6 Center for Allergy Research, Department of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden |
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Abstract: | The dog lipocalin allergen Can f 2 is an important cause of allergic sensitization in humans worldwide. Here, the first crystal structure of recombinant rCan f 2 at 1.45 Å resolution displays a classical lipocalin fold with a conserved Gly-Xaa-Trp motif, in which Trp19 stabilizes the overall topology of the monomeric rCan f 2. Phe38 and Tyr84 localized on the L1 and L5 loops, respectively, control access to the highly hydrophobic calyx. Although the rCan f 2 calyx is nearly identical with the aero-allergens MUP1, Equ c 1 and A2U from mouse, horse and rat, respectively, no IgE cross-reactivity was found using sera from five mono-sensitized subjects. However, clear IgE cross-reactivity was demonstrated between Can f 2 and the cat allergen Fel d 4, although they share less than 22% sequence identity. This suggests a role for these allergens in co-sensitization between cat- and dog-allergic patients. |
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Keywords: | A1M α1-microglobulin A2U α2u globulin/rat urinary protein ApoD apolipoprotein D AP alkaline phosphatase Bos d 2 and Bos d 5 bovine allergens 2 and 5 respectively Can f 1 Can f2 and Can f 3 dog allergens 1 2 and 3 respectively Equ c 1 horse allergen Fel d 1 and Fel d 4 cat allergens HC8γ human complement component-8γ MUP1 mouse urinary protein 1 NGAL neutrophil gelatinase-associated lipocalin RBP retinal-binding protein SCR structurally conserved region Tlc tear lipocalin VEGP von Ebners gland protein |
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