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| - | [[Image:1egj.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1egj| PDB=1egj | SCENE= }} | | {{STRUCTURE_1egj| PDB=1egj | SCENE= }} |
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| - | '''DOMAIN 4 OF THE BETA COMMON CHAIN IN COMPLEX WITH AN ANTIBODY'''
| + | ===DOMAIN 4 OF THE BETA COMMON CHAIN IN COMPLEX WITH AN ANTIBODY=== |
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| - | ==Overview==
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| - | 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)
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10753826}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10753826 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10753826}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Woodcock, J M.]] | | [[Category: Woodcock, J M.]] |
| | [[Category: Cytokine receptor complexed to an antibody]] | | [[Category: Cytokine receptor complexed to an antibody]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:04:29 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 00:39:50 2008'' |
Revision as of 21:39, 30 June 2008
Template:STRUCTURE 1egj
DOMAIN 4 OF THE BETA COMMON CHAIN IN COMPLEX WITH AN ANTIBODY
Template:ABSTRACT PUBMED 10753826
About this Structure
1EGJ is a Protein complex structure of sequences from Homo sapiens and Mus musculus. 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 Tue Jul 1 00:39:50 2008
