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PDBsum entry 1lki
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Contents |
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* Residue conservation analysis
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DOI no:
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Cell
77:1101-1116
(1994)
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PubMed id:
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The crystal structure and biological function of leukemia inhibitory factor: implications for receptor binding.
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R.C.Robinson,
L.M.Grey,
D.Staunton,
H.Vankelecom,
A.B.Vernallis,
J.F.Moreau,
D.I.Stuart,
J.K.Heath,
E.Y.Jones.
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ABSTRACT
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The structure of murine leukemia inhibitory factor (LIF) has been determined by
X-ray crystallography at 2.0 A resolution. The main chain fold conforms to the
four alpha-helix bundle topology previously observed for several members of the
hematopoietic cytokine family. Of these, LIF shows closest structural homology
to granulocyte colony-stimulating factor and growth hormone (GH). Sequence
alignments for the functionally related molecules oncostatin M and ciliary
neurotrophic factor, when mapped to the LIF structure, indicate regions of
conserved surface character. Analysis of the biological function and receptor
specificity of a series of human-mouse LIF chimeras implicate two regions of
receptor interaction that are located in the fourth helix and the preceding
loop. A model for receptor binding based on the structure of the GH
ligand-receptor complex requires additional, novel features to account for these
data.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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S.Chollangi,
J.Wang,
A.Martin,
J.Quinn,
and
J.D.Ash
(2009).
Preconditioning-induced protection from oxidative injury is mediated by leukemia inhibitory factor receptor (LIFR) and its ligands in the retina.
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Neurobiol Dis,
34,
535-544.
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E.J.Hill,
and
A.B.Vernallis
(2008).
Polarized secretion of leukemia inhibitory factor.
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BMC Cell Biol,
9,
53.
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F.Rousseau,
S.Chevalier,
C.Guillet,
E.Ravon,
C.Diveu,
J.Froger,
F.Barbier,
L.Grimaud,
and
H.Gascan
(2008).
Ciliary Neurotrophic Factor, Cardiotrophin-like Cytokine, and Neuropoietin Share a Conserved Binding Site on the Ciliary Neurotrophic Factor Receptor {alpha} Chain.
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J Biol Chem,
283,
30341-30350.
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Y.Ueki,
J.Wang,
S.Chollangi,
and
J.D.Ash
(2008).
STAT3 activation in photoreceptors by leukemia inhibitory factor is associated with protection from light damage.
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J Neurochem,
105,
784-796.
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T.Huyton,
J.G.Zhang,
C.S.Luo,
M.Z.Lou,
D.J.Hilton,
N.A.Nicola,
and
T.P.Garrett
(2007).
An unusual cytokine:Ig-domain interaction revealed in the crystal structure of leukemia inhibitory factor (LIF) in complex with the LIF receptor.
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Proc Natl Acad Sci U S A,
104,
12737-12742.
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PDB code:
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U.Prisco,
C.Leung,
C.Xirouchaki,
C.H.Jones,
J.K.Heath,
and
R.E.Palmer
(2005).
Residue-specific immobilization of protein molecules by size-selected clusters.
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J R Soc Interface,
2,
169-175.
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G.Vlotides,
K.Zitzmann,
G.K.Stalla,
and
C.J.Auernhammer
(2004).
Novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3)/cardiotrophin-like cytokine (CLC)--a novel gp130 cytokine with pleiotropic functions.
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Cytokine Growth Factor Rev,
15,
325-336.
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S.Zvonic,
J.C.Hogan,
P.Arbour-Reily,
R.L.Mynatt,
and
J.M.Stephens
(2004).
Effects of cardiotrophin on adipocytes.
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J Biol Chem,
279,
47572-47579.
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Z.Kondera-Anasz,
J.Sikora,
and
A.Mielczarek-Palacz
(2004).
Leukemia inhibitory factor: an important regulator of endometrial function.
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Am J Reprod Immunol,
52,
97.
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H.Plun-Favreau,
D.Perret,
C.Diveu,
J.Froger,
S.Chevalier,
E.Lelièvre,
H.Gascan,
and
M.Chabbert
(2003).
Leukemia inhibitory factor (LIF), cardiotrophin-1, and oncostatin M share structural binding determinants in the immunoglobulin-like domain of LIF receptor.
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J Biol Chem,
278,
27169-27179.
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J.Bitard,
S.Daburon,
L.Duplomb,
F.Blanchard,
P.Vuisio,
Y.Jacques,
A.Godard,
J.K.Heath,
J.F.Moreau,
and
J.L.Taupin
(2003).
Mutations in the immunoglobulin-like domain of gp190, the leukemia inhibitory factor (LIF) receptor, increase or decrease its affinity for LIF.
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J Biol Chem,
278,
16253-16261.
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L.Vutskits,
E.Gascon,
and
J.Z.Kiss
(2003).
Removal of PSA from NCAM affects the survival of magnocellular vasopressin- and oxytocin-producing neurons in organotypic cultures of the paraventricular nucleus.
|
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Eur J Neurosci,
17,
2119-2126.
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M.J.Boulanger,
A.J.Bankovich,
T.Kortemme,
D.Baker,
and
K.C.Garcia
(2003).
Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130.
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Mol Cell,
12,
577-589.
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PDB code:
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N.Underhill-Day,
L.A.McGovern,
N.Karpovich,
H.J.Mardon,
V.A.Barton,
and
J.K.Heath
(2003).
Functional characterization of W147A: a high-affinity interleukin-11 antagonist.
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Endocrinology,
144,
3406-3414.
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S.K.Nair,
and
S.K.Burley
(2003).
X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors.
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Cell,
112,
193-205.
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PDB codes:
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C.Guillet,
E.Lelièvre,
H.Plun-Favreau,
J.Froger,
M.Chabbert,
J.Hermann,
A.Benoit de Coignac,
J.Y.Bonnefoy,
H.Gascan,
J.F.Gauchat,
and
G.Elson
(2002).
Functionally active fusion protein of the novel composite cytokine CLC/soluble CNTF receptor.
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Eur J Biochem,
269,
1932-1941.
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A.D.Rowan,
P.J.Koshy,
W.D.Shingleton,
B.A.Degnan,
J.K.Heath,
A.B.Vernallis,
J.R.Spaull,
P.F.Life,
K.Hudson,
and
T.E.Cawston
(2001).
Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown.
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Arthritis Rheum,
44,
1620-1632.
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H.Plun-Favreau,
G.Elson,
M.Chabbert,
J.Froger,
O.deLapeyrière,
E.Lelièvre,
C.Guillet,
J.Hermann,
J.F.Gauchat,
H.Gascan,
and
S.Chevalier
(2001).
The ciliary neurotrophic factor receptor alpha component induces the secretion of and is required for functional responses to cardiotrophin-like cytokine.
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EMBO J,
20,
1692-1703.
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J.B.Catterall,
S.Carrère,
P.J.Koshy,
B.A.Degnan,
W.D.Shingleton,
C.E.Brinckerhoff,
J.Rutter,
T.E.Cawston,
and
A.D.Rowan
(2001).
Synergistic induction of matrix metalloproteinase 1 by interleukin-1alpha and oncostatin M in human chondrocytes involves signal transducer and activator of transcription and activator protein 1 transcription factors via a novel mechanism.
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Arthritis Rheum,
44,
2296-2310.
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B.P.Haines,
R.B.Voyle,
and
P.D.Rathjen
(2000).
Intracellular and extracellular leukemia inhibitory factor proteins have different cellular activities that are mediated by distinct protein motifs.
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Mol Biol Cell,
11,
1369-1383.
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G.Middleton,
M.Hamanoue,
Y.Enokido,
S.Wyatt,
D.Pennica,
E.Jaffray,
R.T.Hay,
and
A.M.Davies
(2000).
Cytokine-induced nuclear factor kappa B activation promotes the survival of developing neurons.
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J Cell Biol,
148,
325-332.
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J.Bravo,
and
J.K.Heath
(2000).
Receptor recognition by gp130 cytokines.
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EMBO J,
19,
2399-2411.
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M.C.Deller,
K.R.Hudson,
S.Ikemizu,
J.Bravo,
E.Y.Jones,
and
J.K.Heath
(2000).
Crystal structure and functional dissection of the cytostatic cytokine oncostatin M.
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Structure,
8,
863-874.
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PDB code:
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S.Yao,
D.K.Smith,
M.G.Hinds,
J.G.Zhang,
N.A.Nicola,
and
R.S.Norton
(2000).
Backbone dynamics measurements on leukemia inhibitory factor, a rigid four-helical bundle cytokine.
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Protein Sci,
9,
671-682.
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I.Tacken,
H.Dahmen,
O.Boisteau,
S.Minvielle,
Y.Jacques,
J.Grötzinger,
A.Küster,
U.Horsten,
C.Blanc,
F.A.Montero-Julian,
P.C.Heinrich,
and
G.Müller-Newen
(1999).
Definition of receptor binding sites on human interleukin-11 by molecular modeling-guided mutagenesis.
|
| |
Eur J Biochem,
265,
645-655.
|
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J.Grötzinger,
T.Kernebeck,
K.J.Kallen,
and
S.Rose-John
(1999).
IL-6 type cytokine receptor complexes: hexamer, tetramer or both?
|
| |
Biol Chem,
380,
803-813.
|
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J.L.Taupin,
V.Miossec,
V.Pitard,
F.Blanchard,
S.Daburon,
S.Raher,
Y.Jacques,
A.Godard,
and
J.F.Moreau
(1999).
Binding of leukemia inhibitory factor (LIF) to mutants of its low affinity receptor, gp190, reveals a LIF binding site outside and interactions between the two cytokine binding domains.
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J Biol Chem,
274,
14482-14489.
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K.J.Kallen,
J.Grötzinger,
E.Lelièvre,
P.Vollmer,
D.Aasland,
C.Renné,
J.Müllberg,
K.H.Myer zum Büschenfelde,
H.Gascan,
and
S.Rose-John
(1999).
Receptor recognition sites of cytokines are organized as exchangeable modules. Transfer of the leukemia inhibitory factor receptor-binding site from ciliary neurotrophic factor to interleukin-6.
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J Biol Chem,
274,
11859-11867.
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R.A.Gadient,
and
P.H.Patterson
(1999).
Leukemia inhibitory factor, Interleukin 6, and other cytokines using the GP130 transducing receptor: roles in inflammation and injury.
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Stem Cells,
17,
127-137.
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T.Robak,
A.Wierzbowska,
M.Błasińska-Morawiec,
A.Korycka,
and
J.Z.Błoński
(1999).
Serum levels of IL-6 type cytokines and soluble IL-6 receptors in active B-cell chronic lymphocytic leukemia and in cladribine induced remission.
|
| |
Mediators Inflamm,
8,
277-286.
|
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Y.Senis,
R.Zirngibl,
J.McVeigh,
A.Haman,
T.Hoang,
and
P.A.Greer
(1999).
Targeted disruption of the murine fps/fes proto-oncogene reveals that Fps/Fes kinase activity is dispensable for hematopoiesis.
|
| |
Mol Cell Biol,
19,
7436-7446.
|
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A.R.Horton,
P.F.Barlett,
D.Pennica,
and
A.M.Davies
(1998).
Cytokines promote the survival of mouse cranial sensory neurones at different developmental stages.
|
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Eur J Neurosci,
10,
673-679.
|
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C.F.Ibáñez
(1998).
Emerging themes in structural biology of neurotrophic factors.
|
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Trends Neurosci,
21,
438-444.
|
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D.Kitchen,
R.C.Hoffman,
F.J.Moy,
and
R.Powers
(1998).
Homology model for oncostatin M based on NMR structural data.
|
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Biochemistry,
37,
10581-10588.
|
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F.Blanchard,
S.Raher,
L.Duplomb,
P.Vusio,
V.Pitard,
J.L.Taupin,
J.F.Moreau,
B.Hoflack,
S.Minvielle,
Y.Jacques,
and
A.Godard
(1998).
The mannose 6-phosphate/insulin-like growth factor II receptor is a nanomolar affinity receptor for glycosylated human leukemia inhibitory factor.
|
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J Biol Chem,
273,
20886-20893.
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J.Aikawa,
E.Sato,
S.Kyuwa,
E.Sato,
K.Sasai,
K.Shiota,
and
T.Ogawa
(1998).
Asparagine-linked glycosylation of the rat leukemia inhibitory factor expressed by simian COS7 cells.
|
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Biosci Biotechnol Biochem,
62,
1318-1325.
|
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J.Bravo,
D.Staunton,
J.K.Heath,
and
E.Y.Jones
(1998).
Crystal structure of a cytokine-binding region of gp130.
|
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EMBO J,
17,
1665-1674.
|
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PDB code:
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J.C.Cheetham,
D.M.Smith,
K.H.Aoki,
J.L.Stevenson,
T.J.Hoeffel,
R.S.Syed,
J.Egrie,
and
T.S.Harvey
(1998).
NMR structure of human erythropoietin and a comparison with its receptor bound conformation.
|
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Nat Struct Biol,
5,
861-866.
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PDB code:
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J.L.Taupin,
V.Pitard,
J.Dechanet,
V.Miossec,
N.Gualde,
and
J.F.Moreau
(1998).
Leukemia inhibitory factor: part of a large ingathering family.
|
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Int Rev Immunol,
16,
397-426.
|
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M.F.Towle,
M.Mondragon-Escorpizo,
A.Norin,
and
K.Fukada
(1998).
Deprivation of leukemia inhibitory factor by its function-blocking antibodies augments T cell activation.
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J Interferon Cytokine Res,
18,
387-392.
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M.G.Hinds,
T.Maurer,
J.G.Zhang,
N.A.Nicola,
and
R.S.Norton
(1998).
Solution structure of leukemia inhibitory factor.
|
| |
J Biol Chem,
273,
13738-13745.
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PDB code:
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P.März,
J.G.Cheng,
R.A.Gadient,
P.H.Patterson,
T.Stoyan,
U.Otten,
and
S.Rose-John
(1998).
Sympathetic neurons can produce and respond to interleukin 6.
|
| |
Proc Natl Acad Sci U S A,
95,
3251-3256.
|
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R.J.Duhé,
G.A.Evans,
R.A.Erwin,
R.A.Kirken,
G.W.Cox,
and
W.L.Farrar
(1998).
Nitric oxide and thiol redox regulation of Janus kinase activity.
|
| |
Proc Natl Acad Sci U S A,
95,
126-131.
|
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S.Ozbek,
J.Grötzinger,
B.Krebs,
M.Fischer,
A.Wollmer,
T.Jostock,
J.Müllberg,
and
S.Rose-John
(1998).
The membrane proximal cytokine receptor domain of the human interleukin-6 receptor is sufficient for ligand binding but not for gp130 association.
|
| |
J Biol Chem,
273,
21374-21379.
|
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T.Robak,
A.Gladalska,
H.Stepień,
and
E.Robak
(1998).
Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis.
|
| |
Mediators Inflamm,
7,
347-353.
|
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|
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B.A.Habecker,
A.J.Symes,
N.Stahl,
N.J.Francis,
A.Economides,
J.S.Fink,
G.D.Yancopoulos,
and
S.C.Landis
(1997).
A sweat gland-derived differentiation activity acts through known cytokine signaling pathways.
|
| |
J Biol Chem,
272,
30421-30428.
|
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D.H.Purvis,
and
B.C.Mabbutt
(1997).
Solution dynamics and secondary structure of murine leukemia inhibitory factor: a four-helix cytokine with a rigid CD loop.
|
| |
Biochemistry,
36,
10146-10154.
|
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R.J.Simpson,
A.Hammacher,
D.K.Smith,
J.M.Matthews,
and
L.D.Ward
(1997).
Interleukin-6: structure-function relationships.
|
| |
Protein Sci,
6,
929-955.
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S.W.Thompson,
A.B.Vernallis,
J.K.Heath,
and
J.V.Priestley
(1997).
Leukaemia inhibitory factor is retrogradely transported by a distinct population of adult rat sensory neurons: co-localization with trkA and other neurochemical markers.
|
| |
Eur J Neurosci,
9,
1244-1251.
|
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|
A.Di Marco,
I.Gloaguen,
R.Graziani,
G.Paonessa,
I.Saggio,
K.R.Hudson,
and
R.Laufer
(1996).
Identification of ciliary neurotrophic factor (CNTF) residues essential for leukemia inhibitory factor receptor binding and generation of CNTF receptor antagonists.
|
| |
Proc Natl Acad Sci U S A,
93,
9247-9252.
|
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A.Negro,
and
S.D.Skaper
(1996).
Synthesis, cytotoxic properties and effects on early and late gene induction of a chimeric diphtheria toxin-leukemia-inhibitory factor protein.
|
| |
Eur J Biochem,
241,
507-515.
|
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C.Nishimura,
A.Watanabe,
H.Gouda,
I.Shimada,
and
Y.Arata
(1996).
Folding topologies of human interleukin-6 and its mutants as studied by NMR spectroscopy.
|
| |
Biochemistry,
35,
273-281.
|
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K.R.Hudson,
A.B.Vernallis,
and
J.K.Heath
(1996).
Characterization of the receptor binding sites of human leukemia inhibitory factor and creation of antagonists.
|
| |
J Biol Chem,
271,
11971-11978.
|
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M.Inoue,
C.Nakayama,
and
H.Noguchi
(1996).
Activating mechanism of CNTF and related cytokines.
|
| |
Mol Neurobiol,
12,
195-209.
|
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M.Sendtner,
R.Götz,
B.Holtmann,
J.L.Escary,
Y.Masu,
P.Carroll,
E.Wolf,
G.Brem,
P.Brület,
and
H.Thoenen
(1996).
Cryptic physiological trophic support of motoneurons by LIF revealed by double gene targeting of CNTF and LIF.
|
| |
Curr Biol,
6,
686-694.
|
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P.S.DiStefano,
T.G.Boulton,
J.L.Stark,
Y.Zhu,
K.M.Adryan,
T.E.Ryan,
and
R.M.Lindsay
(1996).
Ciliary neurotrophic factor induces down-regulation of its receptor and desensitization of signal transduction pathways in vivo: non-equivalence with pharmacological activity.
|
| |
J Biol Chem,
271,
22839-22846.
|
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|
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R.A.Hughes,
and
P.D.O'Leary
(1996).
Neurotrophic factors and the development of drugs to promote motoneuron survival.
|
| |
Clin Exp Pharmacol Physiol,
23,
965-969.
|
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R.C.Hoffman,
H.Andersen,
K.Walker,
J.D.Krakover,
S.Patel,
M.R.Stamm,
and
S.G.Osborn
(1996).
Peptide, disulfide, and glycosylation mapping of recombinant human thrombopoietin from ser1 to Arg246.
|
| |
Biochemistry,
35,
14849-14861.
|
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PDB code:
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
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so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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