2NR6

Crystal structure of the complex of antibody and the allergen Bla g 2

Summary for 2NR6

• Entry DOI: 10.2210/pdb2nr6/pdb
• Related: 1YG9
• Descriptor: Aspartic protease Bla g 2, Antibody light chain, Antibody heavy chain, ... (7 entities in total)
• Functional Keywords: bla g 2, fab, hydrolase-immune system complex, hydrolase/immune system
• Biological source: Blattella germanica (German cockroach); More
• Total number of polymer chains: 6
• Total formula weight: 166252.40

Authors

Li, M.,Gustchina, A.,Wlodawer, A.,Pomes, A.,Wunschmann, S. (deposition date: 2006-11-01, release date: 2008-02-19, Last modification date: 2023-08-30)

Primary citation

Li, M.,Gustchina, A.,Alexandratos, J.,Wlodawer, A.,Wunschmann, S.,Kepley, C.L.,Chapman, M.D.,Pomes, A.
Crystal structure of a dimerized cockroach allergen Bla g 2 complexed with a monoclonal antibody.
J.Biol.Chem., 283:22806-22814, 2008

PubMed Abstract: 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-angstroms 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 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 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.

PubMed: 18519566
DOI: 10.1074/jbc.M800937200

Experimental method

X-RAY DIFFRACTION (2.81 Å)