title: Protein structure plays a critical role in peanut allergen stability and may determine immunodominant IgE-binding epitopes.
abstract: Hypersensitivity to peanuts is a reaction mediated by IgE Abs in response to several peanut protein allergens. Among these allergenic proteins, Ara h 2 is one of the most commonly recognized allergens. Ara h 2 is a 17-kDa protein that has eight cysteine residues that could form up to four disulfide bonds. Circular dichroism studies showed substantial changes in the secondary and tertiary structures of the reduced Ara h 2 as compared with the native protein. Upon treatment with trypsin, chymotrypsin, or pepsin, a number of relatively large fragments are produced that are resistant to further enzymatic digestion. These resistant Ara h 2 peptide fragments contain intact IgE-binding epitopes and several potential enzyme cut sites that are protected from the enzymes by the compact structure of the protein. The enzyme-treated allergen remains essentially intact despite the action of proteases until the fragments are dissociated when the disulfide linkages are reduced. Amino acid sequence analysis of the resistant protein fragments indicates that they contain most of the immunodominant IgE-binding epitopes. These results provide a link between allergen structure and the immunodominant IgE-binding epitopes within a population of food-allergic individuals.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Moon
authors.initials: M
authors.lastname: Sen
authors.forename: Randall
authors.initials: R
authors.lastname: Kopper
authors.forename: Laurent
authors.initials: L
authors.lastname: Pons
authors.forename: Edathara C
authors.initials: EC
authors.lastname: Abraham
authors.forename: A Wesley
authors.initials: AW
authors.lastname: Burks
authors.forename: Gary A
authors.initials: GA
authors.lastname: Bannon
mesh_terms: D055516:2S Albumins, Plant; D000485:Allergens / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D010367:Arachis / Q000276:immunology*; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D005512:Food Hypersensitivity / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D016056:Immunodominant Epitopes / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010940:Plant Proteins; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry
chemical_list: D055516:2S Albumins, Plant; D000485:Allergens; D052179:Antigens, Plant; C078642:Ara h II protein, Arachis hypogaea; D004220:Disulfides; D006023:Glycoproteins; D016056:Immunodominant Epitopes; D010940:Plant Proteins; D007073:Immunoglobulin E; D014508:Urea; D010450:Endopeptidases