Barre A, Jacquet G, Sordet C, et al. Homology modelling and conformational analysis of IgE-binding epitopes of Ara h 3 and other legumin allergens with a cupin fold from tree nuts

Surfaces Cellulaires et Signalisation chez les Végétaux, UMR UPS-CNRS 5546, 24 Chemin de Borde Rouge, 31326 Castanet Tolosan, France.
Molecular Immunology (Impact Factor: 2.97). 06/2007; 44(12):3243-55. DOI: 10.1016/j.molimm.2007.01.023
Source: PubMed


Linear IgE-binding epitopes identified in legumin allergens of peanut (Ara h 3) and other allergenic tree nuts (Jug r 4 of walnut, Cor a 9 of hazelnut, Ana o 2 cashew nut) were mapped on three-dimensional models of the proteins built up by homology modelling. A conformational analysis revealed that consensual surface-exposed IgE-binding epitopes exhibited some structural homology susceptible to account for the IgE-binding cross-reactivity observed among peanut and tree nut allergens. This structurally related cross-reactivity seems irrespective of the botanical origin of the allergens and thus demands that persons allergic to peanut avoid other three nuts to prevent possible allergic reactions. IgE-binding epitopes similar to those found in 11S globulin allergens do not apparently occur in other vicilin allergens with the cupin fold from peanut (Ara h 1) or tree nuts (Jug r 2 of walnut, Cor a 1 of hazel nut, Ana o 3 of cashew nut).

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    • "Barre and coworkers mapped linear IgE epitopes identified in Ara h 3, Jug r 4, Cor a 9, and Ana o 2 on three-dimensional models of these allergens built by homology modeling using the Gly m 6 structure 1OD5 from Adachi as a template [57]. The authors’ analyses revealed that these surface-exposed IgE epitopes exhibited some structural similarities, thus accounting for the observed IgE cross-reactivity between peanut and tree nut allergens. "
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    ABSTRACT: Peanut seeds are currently widely used as source of human food ingredients in the United States of America and in European countries due to their high quality protein and oil content. This article describes the classification and molecular biology of peanut seed allergens with particular reference to their cross-reactivities. Currently, the IUIS allergen nomenclature subcommittee accepts 12 peanut allergens. Two allergens belong to the cupin and four to the prolamin superfamily, and six are distributed among profilins, Bet v 1-like proteins, oleosins, and defensins. Clinical observations frequently report an association of peanut allergy with allergies to legumes, tree nuts, seeds, fruits and pollen. Molecular cross-reactivity has been described between members of the Bet v 1-like proteins, the non-specific lipid transfer proteins, and the profilins. This review also addresses the less well-studied cross-reactivity between cupin and prolamin allergens of peanuts and of other plant food sources and the recently discovered cross-reactivity between peanut allergens of unrelated protein families.
    Current Allergy and Asthma Reports 04/2014; 14(4):426. DOI:10.1007/s11882-014-0426-8 · 2.77 Impact Factor
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    • "Moreover, linear epitope maps have been generated for several of these nut 11S globulins, including those from cashew (Wang et al., 2003), walnut (Robotham et al., 2009), and hazelnut (Robotham et al., 2009), as well as from certain oilseed legumes such as peanut (Rabjohn et al., 1999; Rouge et al., 2009) and soybean (Zeece et al., 1999; Helm et al., 2000). The 3D structure of cashew 11S globulin has recently been homologymodeled (Barre et al., 2007; Robotham et al., 2009) based upon extrapolation from the X-ray structure of the soybean 11S globulin (glycinin) (Adachi et al., 2003). The atomic structures of the peanut Ara h 3 and almond prunin-1 homologues have also been recently published and are shown to closely resemble that of soybean (Jin et al., 2009a,b). "
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    ABSTRACT: Both linear and conformational epitopes likely contribute to the allergenicity of tree nut allergens, yet, due largely to technical issues, few conformational epitopes have been characterized. Using the well studied recombinant cashew allergen, Ana o 2, an 11S globulin or legumin, we identified a murine monoclonal antibody which recognizes a conformational epitope and competes with patient IgE Ana o 2-reactive antibodies. This epitope is expressed on the large subunit of Ana o 2, but only when associated with an 11S globulin small subunit. Both Ana o 2 and the homologous soybean Gly m 6 small subunits can foster epitope expression, even when the natural N-terminal to C-terminal subunit order is reversed in chimeric molecules. The epitope, which is also expressed on native Ana o 2, is readily susceptible to destruction by physical and chemical denaturants.
    Molecular Immunology 03/2010; 47(9):1830-8. DOI:10.1016/j.molimm.2009.12.009 · 2.97 Impact Factor
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    • "We have previously described a series of linear epitopes recognized by patients with severe allergic reactions upon cashew nut ingestion (Wang et al., 2003). Homology modeling of cashew 11S globulins revealed that the linear epitopes are dispersed over the large and small subunits and display a range of exposure to solvent (Barre et al., 2007; Robotham et al., 2009). "
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    ABSTRACT: The 11S globulins are members of the cupin protein superfamily and represent an important class of tree nut allergens for which a number of linear epitopes have been mapped. However, specific conformational epitopes for these allergens have yet to be described. We have recently reported a cashew Ana o 2 conformational epitope defined by murine mAb 2B5 and competitively inhibited by a subset of patient IgE antibodies. The 2B5 epitope appears to reside on the large (acidic) subunit, is dependent upon small (basic) subunit association for expression, and is highly susceptible to denaturation. Here we fine map the epitope using a combination of recombinant chimeric cashew Ana o 2-soybean Gly m 6 chimeras, deletion and point mutations, molecular modeling, and electron microscopy of 2B5-Ana o 2 immune complexes. Key residues appear confined to a 24 amino acid segment near the N-terminus of the large subunit peptide, a portion of which makes direct contact with the small subunit. These data provide an explanation for both the small subunit dependence and the structurally labile nature of the epitope.
    Molecular Immunology 03/2010; 47(9):1808-16. DOI:10.1016/j.molimm.2010.01.018 · 2.97 Impact Factor
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