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PDBsum entry 1pvh
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protein metals Protein-protein interface(s) links
Signaling protein/cytokine PDB id
1pvh

 

 

 

 

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Contents
Protein chains
201 a.a. *
169 a.a. *
Metals
IOD ×2
Waters ×192
* Residue conservation analysis
PDB id:
1pvh
Name: Signaling protein/cytokine
Title: Crystal structure of leukemia inhibitory factor in complex with gp130
Structure: Interleukin-6 receptor beta chain. Chain: a, c. Fragment: domains d2 and d3. Synonym: il-6r-beta, interleukin 6 signal transducer, membrane glycoprotein 130, gp130, oncostatin m receptor, cdw130, cd130 antigen. Engineered: yes. Leukemia inhibitory factor. Chain: b, d.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: il6st. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: lif or hilda. Expression_system_taxid: 7108
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.248     R-free:   0.289
Authors: M.J.Boulanger,A.J.Bankovich,T.Kortemme,D.Baker,K.C.Garcia
Key ref:
M.J.Boulanger et al. (2003). Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130. Mol Cell, 12, 577-589. PubMed id: 14527405 DOI: 10.1016/S1097-2765(03)00365-4
Date:
27-Jun-03     Release date:   14-Oct-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P40189  (IL6RB_HUMAN) -  Interleukin-6 receptor subunit beta from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		918 a.a.
201 a.a.
Protein chains
Pfam   ArchSchema ?
P15018  (LIF_HUMAN) -  Leukemia inhibitory factor from Homo sapiens
Seq:
Struc: 		202 a.a.
169 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/S1097-2765(03)00365-4 Mol Cell 12:577-589 (2003)
PubMed id: 14527405  
 
 
Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130.
M.J.Boulanger, A.J.Bankovich, T.Kortemme, D.Baker, K.C.Garcia.
 
  ABSTRACT  
 
Gp130 is a shared cell-surface signaling receptor for at least ten different hematopoietic cytokines, but the basis of its degenerate recognition properties is unknown. We have determined the crystal structure of human leukemia inhibitory factor (LIF) bound to the cytokine binding region (CHR) of gp130 at 2.5 A resolution. Strikingly, we find that the shared binding site on gp130 has an entirely rigid core, while the LIF binding interface diverges sharply in structure and chemistry from that of other gp130 ligands. Dissection of the LIF-gp130 interface, along with comparative studies of other gp130 cytokines, reveal that gp130 has evolved a "thermodynamic plasticity" that is relatively insensitive to ligand structure, to enable crossreactivity. These observations reveal a novel and alternative mechanism for degenerate recognition from that of structural plasticity.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Structural Topology of the LIF/gp130 D2D3 Crystal Structure(A) Backbone structure as viewed from the side of the LIF/gp130 complex.(B) Close-up view of the interface showing four clear spheres of electron density (green) calculated at 2.5 σ from an omit map representing buried solvent molecules.(C) “Top” view of the LIF/gp130 complex showing LIF bound to gp130 through its N-terminal region and the N-terminal flap.(D) Close-up view of omit map electron density contoured at 2.5 σ showing the well-ordered N-terminal flap. Molscript (Kraulis, 1991) and Raster3D (Merritt and Murphy, 1994) were used to prepare secondary structure figures and Bobscript (Esnouf, 1997) was used to prepare electron density figures. 		Figure 5.
Figure 5. Surface Representations Showing the Site III Interfaces of LIF OSM, IL-6, and Viral IL-6The site III LIF and OSM, which engage LIF receptor (LIFR) is defined by both a conserved phenylalanine and a lysine residue. The structural paradigm for site III has been established with hIL-6 (Boulanger et al., 2003) and viral IL-6 (Chow et al., 2001), where the hot spot residue is a single tryptophan that engages the Ig domain of gp130.
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2003, 12, 577-589) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21585315 M.N.Kostjukova, and N.N.Tupitsyn (2011).
Functional Properties of Extracellular Domains of Transducer Receptor gp130.
  Biochemistry (Mosc), 76, 394-406.  
21220115 P.J.Lupardus, G.Skiniotis, A.J.Rice, C.Thomas, S.Fischer, T.Walz, and K.C.Garcia (2011).
Structural snapshots of full-length Jak1, a transmembrane gp130/IL-6/IL-6Rα cytokine receptor complex, and the receptor-Jak1 holocomplex.
  Structure, 19, 45-55.  
20462859 F.Lauck, C.A.Smith, G.F.Friedland, E.L.Humphris, and T.Kortemme (2010).
RosettaBackrub--a web server for flexible backbone protein structure modeling and design.
  Nucleic Acids Res, 38, W569-W575.  
19915009 G.H.Waetzig, A.Chalaris, P.Rosenstiel, J.Suthaus, C.Holland, N.Karl, L.Vallés Uriarte, A.Till, J.Scheller, J.Grötzinger, S.Schreiber, S.Rose-John, and D.Seegert (2010).
N-linked glycosylation is essential for the stability but not the signaling function of the interleukin-6 signal transducer glycoprotein 130.
  J Biol Chem, 285, 1781-1789.  
19920145 S.Le Saux, F.Rousseau, F.Barbier, E.Ravon, L.Grimaud, Y.Danger, J.Froger, S.Chevalier, and H.Gascan (2010).
Molecular dissection of human interleukin-31-mediated signal transduction through site-directed mutagenesis.
  J Biol Chem, 285, 3470-3477.  
19148199 K.C.Garcia, J.J.Adams, D.Feng, and L.K.Ely (2009).
The molecular basis of TCR germline bias for MHC is surprisingly simple.
  Nat Immunol, 10, 143-147.  
19264784 N.Adam, B.Rabe, J.Suthaus, J.Grötzinger, S.Rose-John, and J.Scheller (2009).
Unraveling viral interleukin-6 binding to gp130 and activation of STAT-signaling pathways independently of the interleukin-6 receptor.
  J Virol, 83, 5117-5126.  
19436055 T.R.Hercus, D.Thomas, M.A.Guthridge, P.G.Ekert, J.King-Scott, M.W.Parker, and A.F.Lopez (2009).
The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease.
  Blood, 114, 1289-1298.  
18817510 X.Wang, P.Lupardus, S.L.Laporte, and K.C.Garcia (2009).
Structural biology of shared cytokine receptors.
  Annu Rev Immunol, 27, 29-60.  
18373551 E.Sudarman, M.Bollati-Fogolín, M.Hafner, W.Müller, J.Scheller, S.Rose-John, and J.Eichler (2008).
Synthetic mimetics of the gp130 binding site for viral interleukin-6 as inhibitors of the vIL-6-gp130 interaction.
  Chem Biol Drug Des, 71, 494-500.  
18728012 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.
  J Biol Chem, 283, 30341-30350.  
18775332 G.Skiniotis, P.J.Lupardus, M.Martick, T.Walz, and K.C.Garcia (2008).
Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex.
  Mol Cell, 31, 737-748.
PDB code: 3e0g
18680750 P.J.Lupardus, and K.C.Garcia (2008).
The structure of interleukin-23 reveals the molecular basis of p40 subunit sharing with interleukin-12.
  J Mol Biol, 382, 931-941.
PDB code: 3duh
18926762 Q.Zhang, P.Putheti, Q.Zhou, Q.Liu, and W.Gao (2008).
Structures and biological functions of IL-31 and IL-31 receptors.
  Cytokine Growth Factor Rev, 19, 347-356.  
18243101 S.L.LaPorte, Z.S.Juo, J.Vaclavikova, L.A.Colf, X.Qi, N.M.Heller, A.D.Keegan, and K.C.Garcia (2008).
Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system.
  Cell, 132, 259-272.
PDB codes: 3bpl 3bpn 3bpo
18174171 S.Metz, G.Naeth, P.C.Heinrich, and G.Müller-Newen (2008).
Novel inhibitors for murine and human leukemia inhibitory factor based on fused soluble receptors.
  J Biol Chem, 283, 5985-5995.  
17418792 L.A.Colf, A.J.Bankovich, N.A.Hanick, N.A.Bowerman, L.L.Jones, D.M.Kranz, and K.C.Garcia (2007).
How a single T cell receptor recognizes both self and foreign MHC.
  Cell, 129, 135-146.
PDB codes: 2e7l 2oi9
17437716 R.Matadeen, W.C.Hon, J.K.Heath, E.Y.Jones, and S.Fuller (2007).
The dynamics of signal triggering in a gp130-receptor complex.
  Structure, 15, 441-448.  
17085445 S.Metz, M.Wiesinger, M.Vogt, H.Lauks, G.Schmalzing, P.C.Heinrich, and G.Müller-Newen (2007).
Characterization of the Interleukin (IL)-6 Inhibitor IL-6-RFP: fused receptor domains act as high affinity cytokine-binding proteins.
  J Biol Chem, 282, 1238-1248.  
17652170 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.
  Proc Natl Acad Sci U S A, 104, 12737-12742.
PDB code: 2q7n
17028186 C.Diveu, E.Venereau, J.Froger, E.Ravon, L.Grimaud, F.Rousseau, S.Chevalier, and H.Gascan (2006).
Molecular and functional characterization of a soluble form of oncostatin M/interleukin-31 shared receptor.
  J Biol Chem, 281, 36673-36682.  
16640778 M.Kraich, M.Klein, E.Patiño, H.Harrer, J.Nickel, W.Sebald, and T.D.Mueller (2006).
A modular interface of IL-4 allows for scalable affinity without affecting specificity for the IL-4 receptor.
  BMC Biol, 4, 13.
PDB codes: 2b8u 2b8x 2b8y 2b8z 2b90 2b91 2d48
15722452 A.Schroers, O.Hecht, K.J.Kallen, M.Pachta, S.Rose-John, and J.Grötzinger (2005).
Dynamics of the gp130 cytokine complex: a model for assembly on the cellular membrane.
  Protein Sci, 14, 783-790.  
15861391 D.Perret, F.Rousseau, V.Tran, and H.Gascan (2005).
Reversal of some viral IL-6 electrostatic properties compared to IL-6 contributes to a loss of alpha receptor component recruitment.
  Proteins, 60, 14-26.  
15985167 S.Pletnev, E.Magracheva, A.Wlodawer, and A.Zdanov (2005).
A model of the ternary complex of interleukin-10 with its soluble receptors.
  BMC Struct Biol, 5, 10.  
16293754 X.Wang, M.Rickert, and K.C.Garcia (2005).
Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors.
  Science, 310, 1159-1163.
PDB code: 2b5i
15272019 D.Perret, C.Guillet, G.Elson, J.Froger, H.Plun-Favreau, F.Rousseau, M.Chabbert, J.F.Gauchat, and H.Gascan (2004).
Two different contact sites are recruited by cardiotrophin-like cytokine (CLC) to generate the CLC/CLF and CLC/sCNTFRalpha composite cytokines.
  J Biol Chem, 279, 43961-43970.  
15193311 R.B.Russell, F.Alber, P.Aloy, F.P.Davis, D.Korkin, M.Pichaud, M.Topf, and A.Sali (2004).
A structural perspective on protein-protein interactions.
  Curr Opin Struct Biol, 14, 313-324.  
15563602 S.T.Walsh, J.E.Sylvester, and A.A.Kossiakoff (2004).
The high- and low-affinity receptor binding sites of growth hormone are allosterically coupled.
  Proc Natl Acad Sci U S A, 101, 17078-17083.  
15131306 X.L.He, and K.C.Garcia (2004).
Structure of nerve growth factor complexed with the shared neurotrophin receptor p75.
  Science, 304, 870-875.
PDB code: 1sg1
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data 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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