PDBsum entry 1uc6

Protein binding

PDB id: 1uc6

Contents

Protein chain

109 a.a. *

* Residue conservation analysis

PDB id:

1uc6

Name:

Protein binding

Title:

Solution structure of the carboxyl terminal domain of the ciliary neurotrophic factor receptor

Structure:

Ciliary neurotrophic factor receptor alpha. Chain: a. Fragment: carboxyl terminal domain. Synonym: cntf receptor. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

NMR struc:

21 models

Authors:

D.Man,W.He,K.H.Sze,G.Ke,D.K.Smith,N.Y.Ip,G.Zhu

Key ref:

D.Man et al. (2003). Solution structure of the C-terminal domain of the ciliary neurotrophic factor (CNTF) receptor and ligand free associations among components of the CNTF receptor complex. J Biol Chem, 278, 23285-23294. PubMed id: 12707266 DOI: 10.1074/jbc.M301976200

Date:

08-Apr-03 Release date: 10-Aug-04

Protein chain

P26992  (CNTFR_HUMAN) -  Ciliary neurotrophic factor receptor subunit alpha from Homo sapiens

Seq: 372 a.a.

Struc: 109 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1074/jbc.M301976200

J Biol Chem 278:23285-23294 (2003)

PubMed id: 12707266

Solution structure of the C-terminal domain of the ciliary neurotrophic factor (CNTF) receptor and ligand free associations among components of the CNTF receptor complex.

D.Man, W.He, K.H.Sze, K.Gong, D.K.Smith, G.Zhu, N.Y.Ip.

ABSTRACT

The functional receptor complex of ciliary neurotrophic factor (CNTF), a member of the gp130 family of cytokines, is composed of CNTF, the CNTF receptor alpha (CNTFR), gp130, and the leukemia inhibitory factor receptor (LIFR). However, the nature of the receptor-mediated interactions in this complex has not yet been resolved. To address this issue we have determined the solution structure of the C-terminal or BC domain of CNTFR and studied the interactions of CNTFR with LIFR and gp130. We reported previously that the membrane distal cytokine-binding domain (CBD1) of LIFR could interact in vitro with soluble CNTFR (sCNTFR) in the absence of CNTF. Here we show that the CBD of human gp130 can also bind in vitro to sCNTFR in the absence of CNTF. In addition, the gp130 CBD could compete with the LIFR CBD1 for the binding of sCNTFR. Substitution of residues in the gp130 CBD, the LIFR CBD1, and the CNTFR BC domain that are expected to be involved in receptor-receptor interactions significantly reduced their interactions. An NMR chemical shift perturbation study of the interaction between the BC domains of CNTFR and gp130 further mapped the interaction surface. These data suggest that both the gp130 CBD and the LIFR CBD1 interact with CNTFR in a similar way and provide insights into the nature of the CNTF receptor complex.

Selected figure(s)

Figure 1.
FIG. 1. Schematic representations of the modular structure of CNTFR, gp130, and LIFR. The receptor modules referred to in this study are indicated on the diagrams of the molecules. The BN and the BC domains, which together make up the CBD, contain, respectively, the two conserved disulfide bridges (thin lines) and the WSXWS motif (black bar) that are characteristic of these molecules.

Figure 2.
FIG. 2. Structure of the CNTFR BC domain. A, the ensemble of the lowest 20 energy structures. Each structure was superimposed on the energy-minimized average structure using the backbone atoms of the -strands except for the C' strand. Model 5 is the most representative as defined by NMRCLUST (46). B, ribbon diagram (47), in the same orientation, of the energy-minimized average structure showing the tryptophan-arginine zipper network. In both A and B, the N terminus is at the top of the figure and the C terminus is at the bottom, and the strands are labeled.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 23285-23294) copyright 2003.

Figures were selected by an automated process.