1egj
From Proteopedia
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DOMAIN 4 OF THE BETA COMMON CHAIN IN COMPLEX WITH AN ANTIBODY
Overview
Heterodimeric cytokine receptors generally consist of a major, cytokine-binding subunit and a signaling subunit. The latter can transduce, signals by more than 1 cytokine, as exemplified by the, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2, (IL-2), and IL-6 receptor systems. However, often the signaling subunits, in isolation are unable to bind cytokines, a fact that has made it more, difficult to obtain structural definition of their ligand-binding sites., This report details the crystal structure of the ligand-binding domain of, the GM-CSF/IL-3/IL-5 receptor beta-chain (beta(c)) signaling subunit in, complex with the Fab fragment of the antagonistic monoclonal antibody, BION-1. This is the first single antagonist of all 3 known, eosinophil-producing cytokines, and it is therefore capable of regulating, eosinophil-related diseases such as asthma. The structure reveals a, fibronectin type III domain, and the antagonist-binding site involves, major contributions from the loop between the B and C strands and overlaps, the cytokine-binding site. Furthermore, tyrosine(421) (Tyr(421)), a key, residue involved in receptor activation, lies in the neighboring loop, between the F and G strands, although it is not immediately adjacent to, the cytokine-binding residues in the B-C loop. Interestingly, functional, experiments using receptors mutated across these loops demonstrate that, they are cooperatively involved in full receptor activation. The, experiments, however, reveal subtle differences between the B-C loop and, Tyr(421), which is suggestive of distinct functional roles. The, elucidation of the structure of the ligand-binding domain of beta(c) also, suggests how different cytokines recognize a single receptor subunit, which may have implications for homologous receptor systems. (Blood., 2000;95:2491-2498)
About this Structure
1EGJ is a Protein complex structure of sequences from Homo sapiens and Mus musculus with NAG as ligand. Full crystallographic information is available from OCA.
Reference
Structure of the activation domain of the GM-CSF/IL-3/IL-5 receptor common beta-chain bound to an antagonist., Rossjohn J, McKinstry WJ, Woodcock JM, McClure BJ, Hercus TR, Parker MW, Lopez AF, Bagley CJ, Blood. 2000 Apr 15;95(8):2491-8. PMID:10753826
Page seeded by OCA on Mon Nov 12 16:43:22 2007
