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Structural basis for cross-reactivity and conformation fluctuation of the major beech pollen allergen Fag s 1.

ABSTRACT: Fag s 1 is a member of the Pathogen Related protein family 10 (PR-10) and can elicit cross-reaction with IgE antibodies produced against the birch pollen allergen Bet v 1. The Nuclear Magnetic Resonance (NMR) structure of Fag s 1 is presented along with its dynamic properties. It shares 66% identity with Bet v 1 and exhibits the expected three ?-helices and seven ?-sheets arranged as a semi-beta barrel and exposing the residues mapped as the Bet v 1 IgE epitope. The structural dynamics of Fag s 1 were monitored on the fast and intermediate timescales, using relaxation rates. The complex dynamics of Fag s 1 are closely related to the internal cavity, and they modulate IgE and ligand binding.

SUBMITTER: Moraes AH

PROVIDER: S-EPMC6043577 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Structural basis for cross-reactivity and conformation fluctuation of the major beech pollen allergen Fag s 1.

Moraes Adolfo H AH Asam Claudia C Almeida Fabio C L FCL Wallner Michael M Ferreira Fatima F Valente Ana Paula AP

Scientific reports 20180712 1

Fag s 1 is a member of the Pathogen Related protein family 10 (PR-10) and can elicit cross-reaction with IgE antibodies produced against the birch pollen allergen Bet v 1. The Nuclear Magnetic Resonance (NMR) structure of Fag s 1 is presented along with its dynamic properties. It shares 66% identity with Bet v 1 and exhibits the expected three α-helices and seven β-sheets arranged as a semi-beta barrel and exposing the residues mapped as the Bet v 1 IgE epitope. The structural dynamics of Fag s ...[more]

PMID: 30002383

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Ligand binding modulates the structural dynamics and compactness of the major birch pollen allergen.

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High-Yield Production of the Major Birch Pollen Allergen Bet v 1 With Allergen Immunogenicity in Nicotiana benthamiana.

Project description:Type I allergy is an immunological disorder triggered by allergens and causes significant health problems. The major allergen of birch pollen is Bet v 1, which belongs to the pathogen-related protein 10 (PR-10) family. Here, we established a rapid and robust method for the production of Bet v 1 in Nicotiana benthamiana leaves, with binding activity to allergic patients' IgE. The Bet v 1 allergen was expressed in N. benthamiana using a strong agroinfiltration-based transient protein expression system, which consists of a deconstructed geminiviral vector system with a double terminator. Five days post-infiltration, the allergen concentration in N. benthamiana leaves was 1.2 mg/g of fresh mass, being this the maximum yield of Bet v 1 in plants reported up to now. A part of plant-derived Bet v 1 was glycosylated. Bet v 1 purified from N. benthamiana or Brevibacillus brevis was used to carry out enzyme-linked immunoassays; both recombinant allergens were found to have comparable binding properties to the IgE of allergic patients. These results suggest that our plant expression system allows rapid and robust production of the allergen, which keeps the immunogenicity.

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In silico analysis of a major allergen from Rattus norvegicus, Rat n 1, and cross-reactivity with domestic pets.

Project description:Background: Lipocalins play a role in the cellular trafficking of pheromones and are involved in allergic responses to domestic pets. However, the cross-reactivity among allergens of this group has been poorly explored, and the pheromone linking capacity is not well characterized. The aim of this study was to explore cross-reactive epitopes and pheromone linking capacity among Rat n 1 and homologues in domestic pets through an in silico approach. Methods: ElliPro and BepiPred in silico tools were used to predict B cell linear and cross-reactive epitopes. The pheromone linking capacity was explored by docking virtual screening with 2-ethylhexanol, 2,5-dimethylpyrazine, 2-sec-butyl-4,5-dihydrothiazole, and 2-heptanone ligands. Results: According to the analysis, Rat n 1 shares 52% identity with Equ c 1, Can f 6, Fel d 4, and Mus m 1 allergens. The overlapping structures analysis revealed high structural homology (root mean square deviation < 1). Four lineal and three discontinuous epitopes were predicted on Ra t n 1. A lineal epitope located between amino acids residues 24 and 36 was highly conserved on all allergens explored. A cross-reactive discontinuous epitope (T142, K143, D144, L145, S146, S147, D148, K152, L170, T171, T173, D174) was also found. Docking molecular simulations revealed the region involved in linking ligands, and we identified the properties of the binding of four pheromones and the binding potential of Rat n 1. Critical residues for interactions are reported in this study. Conclusions: We identified some possible allergens from Rattus norvegicus, and those allergens could have cross-reactivity with allergens from some animals. The results need to be confirmed with in vitro studies and could be utilized to contribute to immunotherapy and reduce allergic diseases related to lipocalins.

| S-EPMC7194344 | biostudies-literature

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