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Publication Abstract from PubMed

Gene deletion studies in mice have revealed critical roles for interleukins-4 and -13 in asthma development, with the latter controlling lung airways resistance and mucous secretion. We have now developed human neutralizing monoclonal antibodies against the human IL-13 receptor alpha1 subunit that prevent activation of the receptor complex by both IL-4 and IL-13. We describe the crystal structures of the Fab fragment of antibody 10G5H6 alone and in complex with the ectodomain 3 (D3) of the IL-13Ralpha1. Although the structure showed significant domain swapping within a D3 dimer we showed that Arg230, Phe233, Tyr250, Gln252 and Leu293 in each D3 monomer and Ser32, Asn102, and Trp103 in 10G5H6 Fab are the key interacting residues at the interface of the D3:10G5H6 Fab complex. One of the most striking contacts is the insertion of the ligand-contacting residue Leu293 of D3 into a deep pocket on the surface of 10G5H6 Fab and this appears to be a central determinant of the high binding affinity and neutralizing activity of the antibody.

Production of a human neutralizing monoclonal antibody and its crystal structure in complex with the ectodomain 3 of the interleukin-13 receptor alpha1.,Redpath NT, Xu Y, Wilson NJ, Andrews AE, Fabri LJ, Baca M, Braley H, Lu P, Ireland C, Ernst RE, Woods A, Forrest G, An Z, Zaller DM, Strohl WR, Luo CS, Czabotar PE, Garrett TP, Hilton DJ, Nash AD, Zhang JG, Nicola NA Biochem J. 2013 Feb 6. PMID:23384096^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.