4hwb

Crystal structure of ectodomain 3 of the IL-13 receptor alpha 1 in complex with a human neutralizing monoclonal antibody fragment

spinqualitylabelsall models 4hwb, resolution 2.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hwb is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.61Å Ligands: NHE, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function I13R1_HUMAN Binds with low affinity to interleukin-13 (IL13). Together with IL4RA can form a functional receptor for IL13. Also serves as an alternate accessory protein to the common cytokine receptor gamma chain for interleukin-4 (IL4) signaling, but cannot replace the function of IL2RG in allowing enhanced interleukin-2 (IL2) binding activity. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Interleukin receptor 3D structures Monoclonal Antibodies 3D structures

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