Crystal Structure of a Dimerized Cockroach Allergen Bla g 2 Complexed with a Monoclonal Antibody
العنوان: | Crystal Structure of a Dimerized Cockroach Allergen Bla g 2 Complexed with a Monoclonal Antibody |
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المؤلفون: | Alla Gustchina, Anna Pomés, Christopher L. Kepley, Alexander Wlodawer, Jerry Alexandratos, Sabina Wünschmann, Martin D. Chapman, Mi Li |
المصدر: | Journal of Biological Chemistry. 283:22806-22814 |
بيانات النشر: | Elsevier BV, 2008. |
سنة النشر: | 2008 |
مصطلحات موضوعية: | medicine.drug_class, Stereochemistry, Dimer, Lysine, Mutant, Cockroaches, Biology, Arginine, Crystallography, X-Ray, Monoclonal antibody, Biochemistry, Epitope, law.invention, chemistry.chemical_compound, law, Hypersensitivity, medicine, Animals, Aspartic Acid Endopeptidases, Humans, Molecular Biology, Monoclonal Antibody 7C11, Antibodies, Monoclonal, Cell Biology, Recombinant Proteins, chemistry, Protein Structure and Folding, biology.protein, Recombinant DNA, Insect Proteins, Tyrosine, Antibody, Dimerization |
الوصف: | 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-Å resolution. Bla g 2 binds to the antibody through four loops that include residues 60-70, 83-86, 98-100, and 129-132. Cation-π 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 α-helix and a helical turn from each allergen monomer, exhibiting a novel dimerization mode for 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 β-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. |
تدمد: | 0021-9258 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9a0645d62a475cebd1b806b3735e1b00Test https://doi.org/10.1074/jbc.m800937200Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....9a0645d62a475cebd1b806b3735e1b00 |
قاعدة البيانات: | OpenAIRE |
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