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|Title:||The solution structure of the cytokine-binding domain of the common -chain of the receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5|
|Citation:||Journal of Molecular Biology, 2000; 297(4):989-1001|
|Publisher:||Academic Press Ltd|
|Abstract:||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.|
|Keywords:||Humans; Arginine; Tryptophan; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Receptors, Interleukin-3; Receptors, Interleukin; Cytokines; Solutions; Nuclear Magnetic Resonance, Biomolecular; Binding Sites; Amino Acid Sequence; Amino Acid Motifs; Conserved Sequence; Protein Structure, Secondary; Protein Structure, Tertiary; Models, Molecular; Molecular Sequence Data; Receptors, Interleukin-5|
|Appears in Collections:||Molecular and Biomedical Science publications|
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