Journal article
Production of a human neutralizing monoclonal antibody and its crystal structure in complex with ectodomain 3 of the interleukin-13 receptor α1
NT Redpath, Y Xu, NJ Wilson, LJ Fabri, M Baca, AE Andrews, H Braley, P Lu, C Ireland, RE Ernst, A Woods, G Forrest, Z An, DM Zaller, WR Strohl, CS Luo, PE Czabotar, TPJ Garrett, DJ Hilton, AD Nash Show all
Biochemical Journal | Published : 2013
DOI: 10.1042/BJ20121819
Abstract
Gene deletion studies in mice have revealed critical roles for IL (interleukin)-4 and -13 in asthma development, with the latter controlling lung airways resistance and mucus secretion. We have now developed human neutralizing monoclonal antibodies against human IL-13Rα1 (IL-13 receptor α1) 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 D3 (ectodomain 3) of IL-13Rα1. Although the structure showed significant domain swapping within aD3 dimer,we showed thatArg 230, Phe233, Tyr250, Gln252 and Leu 293 in each D3 monomer and Ser32, Asn102 and Trp103 in 10G5H6 Fab ar..
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Awarded by Merck, Sharp Dohme Research
Awarded by Australian National Health and Medical Research Council
Funding Acknowledgements
The work was supported by a Merck, Sharp & Dohme Research Grant (2009-2010), the Australian National Health and Medical Research Council [grant numbers 257500 and 461219], the Australian Cancer Research Foundation, the Victoria Government Operational Infrastructure Scheme, and the Australian Government Independent Research Institutes Infrastructure Support Scheme.