Evaluating pH-induced gastrointestinal aggregation of Arachis hypogaea 1 fragments as potential components of peanut allergy.
The seed storage glycoprotein Arachis hypogaea (Ara h) 1 is a major allergen found in peanuts. The biochemical resistance of food proteins to protease digestion contributes to their allergenicity. The rapid proteolysis of Ara h 1 under gastric conditions challenges this model. Biophysical and in vitro digestion experiments were carried out to identify how Ara h 1 epitopes might survive digestion, despite their facile degradation. The bicupin core of Ara h 1 can be unfolded at low pH and reversibly folded at higher pH. Additionally, peptide fragments from simulated gastric digestion predominantly form noncovalent aggregates when transferred to base. Disulfide cross-links within these aggregates occur as intermediates in relatively low amounts only at early times and play no role in shielding peptides from degradation. It is proposed that peptide fragments which survive gastric conditions form large aggregates in basic environments such as the small intestine, making epitopes available for triggering an allergic response.
Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey , 679 Hoes Lane, Piscataway, New Jersey 08854, United States.
I John
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Khan
Rong
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Priyesh
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Patel
Vikas
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Nanda
D052179:Antigens, Plant / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010367:Arachis / Q000737:chemistry / Q000276:immunology; D004063:Digestion; D000939:Epitopes / Q000276:immunology; D041981:Gastrointestinal Tract / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins; D021183:Peanut Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010940:Plant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D017510:Protein Folding
D052179:Antigens, Plant; C500889:Ara h 1 protein, Arachis hypogaea; D000939:Epitopes; D006023:Glycoproteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D010940:Plant Proteins; D010434:Pepsin A