1c8p
NMR STRUCTURE OF THE LIGAND BINDING DOMAIN OF THE COMMON BETA-CHAIN IN THE GM-CSF, IL-3 AND IL-5 RECEPTORS
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OverviewOverview
The haemopoietic cytokines, granulocyte-macrophage colony-stimulating, factor, interleukin-3 and interleukin-5 bind to cell-surface receptors, comprising ligand-specific alpha-chains and a shared beta-chain. The, beta-chain is the critical signalling subunit of the receptor and its, fourth domain not only plays a critical role in interactions with ligands, hence in receptor activation, but also contains residues whose mutation, can lead to ligand-independent activation of the receptor. We have, determined the NMR solution structure of the isolated human fourth domain, of the beta-chain. The protein has a fibronectin type III fold with a, well-defined hydrophobic core and is stabilised by an extensive network of, pi-cation interactions involving Trp and Arg side-chains, including two, Trp residues outside the highly conserved Trp-Ser-Xaa-Trp-Ser motif (where, Xaa is any amino acid) that is found in many cytokine receptors. Most of, the residues implicated in factor-independent mutants localise to the, rigid core of the domain or the pi-cation stack. The loops between the B, and C, and the F and G strands, that contain residues important for, interactions with cytokines, lie adjacent at the membrane-distal end of, the domain, consistent with their being involved cooperatively in binding, cytokines. The elucidation of the structure of the cytokine-binding domain, of the beta-chain provides insight into the cytokine-dependent and, factor-independent activation of the receptor.
About this StructureAbout this Structure
1C8P is a Single protein structure of sequence from Homo sapiens. This structure superseeds the now removed PDB entry 1D4Q. Full crystallographic information is available from OCA.
ReferenceReference
The solution structure of the cytokine-binding domain of the common beta-chain of the receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5., Mulhern TD, Lopez AF, D'Andrea RJ, Gaunt C, Vandeleur L, Vadas MA, Booker GW, Bagley CJ, J Mol Biol. 2000 Apr 7;297(4):989-1001. PMID:10736232
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