The amyloid fold of Gad m 1 epitopes governs IgE binding.
Amyloids are polymeric structural states formed from locally or totally unfolded protein chains that permit surface reorganizations, stability enhancements and interaction properties that are absent in the precursor monomers. β-Parvalbumin, the major allergen in fish allergy, forms amyloids that are recognized by IgE in the patient sera, suggesting a yet unknown pathological role for these assemblies. We used Gad m 1 as the fish β-parvalbumin model and a combination of approaches, including peptide arrays, recombinant wt and mutant chains, biophysical characterizations, protease digestions, mass spectrometry, dot-blot and ELISA assays to gain insights into the role of amyloids in the IgE interaction. We found that Gad m 1 immunoreactive regions behave as sequence-dependent conformational epitopes that provide a 1000-fold increase in affinity and the structural repetitiveness required for optimal IgE binding and cross-linking upon folding into amyloids. These findings support the amyloid state as a key entity in type I food allergy.
Instituto de Química Física "Rocasolano", Consejo Superior de Investigaciones Científicas, 28006 Madrid, Spain.
Rosa
R
Sánchez
Instituto de Química Física "Rocasolano", Consejo Superior de Investigaciones Científicas, 28006 Madrid, Spain.
Javier
J
Martínez
Instituto de Química Médica, Consejo Superior de Investigaciones Científicas, 28006 Madrid, Spain.
Ana
A
Castro
Departamento de Alergología, Hospital Universitario La Paz, 28046 Madrid, Spain.|Instituto de Investigación-Hospital Universitario La Paz (IdiPaz), 28046 Madrid, Spain.
María
M
Pedrosa
Departamento de Alergología, Hospital Universitario La Paz, 28046 Madrid, Spain.|Instituto de Investigación-Hospital Universitario La Paz (IdiPaz), 28046 Madrid, Spain.
Santiago
S
Quirce
Instituto de Investigación-Hospital Universitario La Paz (IdiPaz), 28046 Madrid, Spain.
Rosa
R
Rodríguez-Pérez
Instituto de Química Física "Rocasolano", Consejo Superior de Investigaciones Científicas, 28006 Madrid, Spain.
María
M
Gasset
D000485:Allergens / Q000378:metabolism; D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism*; D058227:Amyloidogenic Proteins / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism; D000818:Animals; D002648:Child; D000939:Epitopes / Q000378:metabolism*; D005260:Female; D005399:Fishes; D005512:Food Hypersensitivity / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D008297:Male; D010320:Parvalbumins / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology
D000485:Allergens; D000682:Amyloid; D058227:Amyloidogenic Proteins; D000939:Epitopes; D010320:Parvalbumins; D007073:Immunoglobulin E