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PDBsum entry 1uc6
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Protein binding
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PDB id
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1uc6
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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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.
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Authors
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D.Man,
W.He,
K.H.Sze,
K.Gong,
D.K.Smith,
G.Zhu,
N.Y.Ip.
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Ref.
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J Biol Chem, 2003,
278,
23285-23294.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2003,
278,
23285-23294)
copyright 2003.
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