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https://hdl.handle.net/2440/28001
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Type: | Journal article |
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 |
Author: | Mulhern, T. Lopez, A. D'Andrea, R. Gaunt, C. Vandeleur, L. Vadas, M. Booker, G. Bagley, C. |
Citation: | Journal of Molecular Biology, 2000; 297(4):989-1001 |
Publisher: | Academic Press Ltd |
Issue Date: | 2000 |
ISSN: | 0022-2836 1089-8638 |
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 |
DOI: | 10.1006/jmbi.2000.3610 |
Published version: | http://dx.doi.org/10.1006/jmbi.2000.3610 |
Appears in Collections: | Aurora harvest 2 Molecular and Biomedical Science publications |
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