1C8P

NMR STRUCTURE OF THE LIGAND BINDING DOMAIN OF THE COMMON BETA-CHAIN IN THE GM-CSF, IL-3 AND IL-5 RECEPTORS

Replaces:  1D4Q

Summary for 1C8P

• Entry DOI: 10.2210/pdb1c8p/pdb
• Descriptor: CYTOKINE RECEPTOR COMMON BETA CHAIN (1 entity in total)
• Functional Keywords: beta sandwich, cytokine receptor, fn3 domain, membrane protein
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P32927
• Total number of polymer chains: 1
• Total formula weight: 12122.48

Authors

Mulhern, T.D.,D'Andrea, R.J.,Gaunt, C.,Vandeleur, L.,Vadas, M.A.,Lopez, A.F.,Booker, G.W.,Bagley, C.J. (deposition date: 1999-10-05, release date: 2000-06-15, Last modification date: 2023-12-27)

Primary citation

Mulhern, T.D.,Lopez, A.F.,D'Andrea, R.J.,Gaunt, C.,Vandeleur, L.,Vadas, M.A.,Booker, G.W.,Bagley, C.J.
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., 297:989-1001, 2000

PubMed 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.

PubMed: 10736232
DOI: 10.1006/jmbi.2000.3610

Experimental method

SOLUTION NMR