title: Solution and high-pressure NMR studies of the structure, dynamics, and stability of the cross-reactive allergenic cod parvalbumin Gad m 1.
abstract: Beta-parvalbumins from different fish species have been identified as the main elicitors of IgE-mediated reactions in fish-allergic individuals. Here, we report for the first time the NMR determination of the structure and dynamics of the major Atlantic cod (Gadus morhua) allergen Gad m 1 and compare them with other known parvalbumins. Although the Gad m 1 structure and accessibility of putative IgE epitopes are similar to parvalbumins in mackerel and carp, the charge distribution at the putative epitopes is different. The determination of the Gad m 1 structure contributes to a better understanding of cross-reactivity among fish parvalbumins. In addition, the high-pressure NMR and temperature variation experiments revealed the important contribution of the AB motif and other regions to the protein folding. This structural information could assist the future identification of hot spots for targeted mutations to develop hypoallergenic Ca(2+) -free forms for potential use in immunotherapy.
authors.affiliation: Department of Structural Biology, Institute of Medical Biochemistry, National Center of Nuclear Magnetic Resonance, Federal University of Rio de Janeiro, Brazil.
authors.forename: Adolfo H
authors.initials: AH
authors.lastname: Moraes
authors.forename: Daniela
authors.initials: D
authors.lastname: Ackerbauer
authors.forename: Maria
authors.initials: M
authors.lastname: Kostadinova
authors.forename: Merima
authors.initials: M
authors.lastname: Bublin
authors.forename: Guilherme Augusto
authors.initials: GA
authors.lastname: de Oliveira
authors.forename: Fátima
authors.initials: F
authors.lastname: Ferreira
authors.forename: Fabio C L
authors.initials: FC
authors.lastname: Almeida
authors.forename: Heimo
authors.initials: H
authors.lastname: Breiteneder
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Valente
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D003429:Cross Reactions; D029941:Fish Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D048389:Gadus morhua; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010320:Parvalbumins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011312:Pressure; D011487:Protein Conformation; D055550:Protein Stability; D012996:Solutions; D040681:Structural Homology, Protein; D013696:Temperature
chemical_list: D000485:Allergens; D029941:Fish Proteins; D010320:Parvalbumins; D012996:Solutions; D002118:Calcium
keywords: allergenicity; cross-reactivity; high-pressure NMR; protein structure; β-parvalbumin