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Title: The novel structure of the cockroach allergen Bla g 1 has implications for allergenicity and exposure assessment

Authors:
; ; ; ; ; ; ; ;  [1];  [2]
  1. INDOOR
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
INDUSTRYNIHNIAID
OSTI Identifier:
1258699
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Allergy and Clinical Immunology; Journal Volume: 132; Journal Issue: 6
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Mueller, Geoffrey A., Pedersen, Lars C., Lih, Fred B., Glesner, Jill, Moon, Andrea F., Chapman, Martin D., Tomer, Kenneth B., London, Robert E., Pomés, Anna, and NIEHS). The novel structure of the cockroach allergen Bla g 1 has implications for allergenicity and exposure assessment. United States: N. p., 2016. Web. doi:10.1016/j.jaci.2013.06.014.
Mueller, Geoffrey A., Pedersen, Lars C., Lih, Fred B., Glesner, Jill, Moon, Andrea F., Chapman, Martin D., Tomer, Kenneth B., London, Robert E., Pomés, Anna, & NIEHS). The novel structure of the cockroach allergen Bla g 1 has implications for allergenicity and exposure assessment. United States. doi:10.1016/j.jaci.2013.06.014.
Mueller, Geoffrey A., Pedersen, Lars C., Lih, Fred B., Glesner, Jill, Moon, Andrea F., Chapman, Martin D., Tomer, Kenneth B., London, Robert E., Pomés, Anna, and NIEHS). 2016. "The novel structure of the cockroach allergen Bla g 1 has implications for allergenicity and exposure assessment". United States. doi:10.1016/j.jaci.2013.06.014.
@article{osti_1258699,
title = {The novel structure of the cockroach allergen Bla g 1 has implications for allergenicity and exposure assessment},
author = {Mueller, Geoffrey A. and Pedersen, Lars C. and Lih, Fred B. and Glesner, Jill and Moon, Andrea F. and Chapman, Martin D. and Tomer, Kenneth B. and London, Robert E. and Pomés, Anna and NIEHS)},
abstractNote = {},
doi = {10.1016/j.jaci.2013.06.014},
journal = {Journal of Allergy and Clinical Immunology},
number = 6,
volume = 132,
place = {United States},
year = 2016,
month = 7
}
  • No abstract prepared.
  • The crystal structure of Bla g 2 was solved in order to investigate the structural basis for the allergenic properties of this unusual protein. This is the first structure of an aspartic protease in which conserved glycine residues, in two canonical DTG triads, are substituted by different amino acid residues. Another unprecedented feature revealed by the structure is the single phenylalanine residue insertion on the tip of the flap, with the side-chain occupying the S1 binding pocket. This and other important amino acid substitutions in the active site region of Bla g 2 modify the interactions in the vicinity ofmore » the catalytic aspartate residues, increasing the distance between them to {approx}4 {angstrom} and establishing unique direct contacts between the flap and the catalytic residues. We attribute the absence of substantial catalytic activity in Bla g 2 to these unusual features of the active site. Five disulfide bridges and a Zn-binding site confer stability to the protein, which may contribute to sensitization at lower levels of exposure than other allergens.« less
  • The crystal structure of a 1:1 complex between the German cockroach allergen Bla g 2 and the Fab' fragment of a monoclonal antibody 7C11 was solved at 2.8-{angstrom} resolution. Bla g 2 binds to the antibody through four loops that include residues 60-70, 83-86, 98-100, and 129-132. Cation-{pi} interactions exist between Lys-65, Arg-83, and Lys-132 in Bla g 2 and several tyrosines in 7C11. In the complex with Fab', Bla g 2 forms a dimer, which is stabilized by a quasi-four-helix bundle comprised of an {alpha}-helix and a helical turn from each allergen monomer, exhibiting a novel dimerization mode formore » an aspartic protease. A disulfide bridge between C51a and C113, unique to the aspartic protease family, connects the two helical elements within each Bla g 2 monomer, thus facilitating formation of the bundle. Mutation of these cysteines, as well as the residues Asn-52, Gln-110, and Ile-114, involved in hydrophobic interactions within the bundle, resulted in a protein that did not dimerize. The mutant proteins induced less {beta}-hexosaminidase release from mast cells than the wild-type Bla g 2, suggesting a functional role of dimerization in allergenicity. Because 7C11 shares a binding epitope with IgE, the information gained by analysis of the crystal structure of its complex provided guidance for site-directed mutagenesis of the allergen epitope. We have now identified key residues involved in IgE antibody binding; this information will be useful for the design of vaccines for immunotherapy.« less
  • No abstract prepared.