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1c8p
From Proteopedia
| 1c8p, 20 NMR models () | |||||||||
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| Domains: | FN3 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
NMR STRUCTURE OF THE LIGAND BINDING DOMAIN OF THE COMMON BETA-CHAIN IN THE GM-CSF, IL-3 AND IL-5 RECEPTORS
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1C8P is a 1 chain structure of sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1d4q. Full experimental information is available from OCA.
Reference
- Mulhern TD, Lopez AF, D'Andrea RJ, Gaunt C, Vandeleur L, Vadas MA, Booker GW, Bagley CJ. 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. J Mol Biol. 2000 Apr 7;297(4):989-1001. PMID:10736232 doi:10.1006/jmbi.2000.3610
Page seeded by OCA on Mon Feb 16 20:56:44 2009
