PDBsum entry 1c8p

Membrane protein

PDB id: 1c8p

Contents

Protein chain

102 a.a. *

* Residue conservation analysis

PDB id:

1c8p

Name:

Membrane protein

Title:

Nmr structure of the ligand binding domain of the common beta-chain in the gm-csf, il-3 and il-5 receptors

Structure:

Cytokine receptor common beta chain. Chain: a. Fragment: domain 4. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell: hemopoietic cells. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

T.D.Mulhern,R.J.D'Andrea,C.Gaunt,L.Vandeleur,M.A.Vadas,A.F.Lopez, G.W.Booker,C.J.Bagley

Key ref:

T.D.Mulhern et al. (2000). 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. PubMed id: 10736232 DOI: 10.1006/jmbi.2000.3610

Date:

05-Oct-99 Release date: 15-Jun-00

Supersedes:

1d4q

Protein chain

P32927  (IL3RB_HUMAN) -  Cytokine receptor common subunit beta from Homo sapiens

Seq: 897 a.a.

Struc: 102 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1006/jmbi.2000.3610

J Mol Biol 297:989 (2000)

PubMed id: 10736232

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.

T.D.Mulhern, A.F.Lopez, R.J.D'Andrea, C.Gaunt, L.Vandeleur, M.A.Vadas, G.W.Booker, C.J.Bagley.

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.

Selected figure(s)

Figure 3.
Figure 3. A stereo view of the D4b[c] residues that, when mutated, cause factor-independence. The side-chains are displayed and labelled. The Ile and Leu residues (yellow), the Trp and Tyr residues (orange) and the Gln (green). The structural elements are coloured as in Figure 1. The susceptible residues form a contiguous tight cluster including buried and surface-exposed residues.

Figure 5.
Figure 5. Residues critical to cytokine-binding. A stereo view of the minimised average structure showing the position of residues found to be important for high-affinity ligand-binding. The critical residues are located in the F-G loop, Tyr421 (green), and in the B-C loop, Tyr365 (yellow), His367 (orange) and Ile368 (red). The structural elements are coloured as in Figure 1.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 297, 989-0) copyright 2000.

Figures were selected by an automated process.