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Cytokine PDB id
1pgr
Jmol
Contents
Protein chains
161 a.a. *
208 a.a. *
165 a.a. *
* Residue conservation analysis
PDB id:
1pgr
Name: Cytokine
Title: 2:2 complex of g-csf with its receptor
Structure: Protein (granulocyte colony-stimulating factor). Chain: a, c, e, g. Synonym: g-csf. Engineered: yes. Protein (g-csf receptor). Chain: b, d, f, h. Fragment: crh region (bn domain:h1-108, bc domain:h109- 215). Synonym: g-csf-r.
Source: Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: extracellular. Expressed in: escherichia coli. Expression_system_taxid: 562. Mus musculus. House mouse. Organism_taxid: 10090.
Biol. unit: Octamer (from PQS)
Resolution:
3.50Å     R-factor:   0.317    
Authors: M.Aritomi,N.Kunishima,T.Okamoto,R.Kuroki,Y.Ota,K.Morikawa
Key ref:
M.Aritomi et al. (1999). Atomic structure of the GCSF-receptor complex showing a new cytokine-receptor recognition scheme. Nature, 401, 713-717. PubMed id: 10537111 DOI: 10.1038/44394
Date:
08-Mar-99     Release date:   08-Mar-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P09919  (CSF3_HUMAN) -  Granulocyte colony-stimulating factor
Seq:
Struc: 		207 a.a.
161 a.a.
Protein chains
Pfam   ArchSchema ?
P40223  (CSF3R_MOUSE) -  Granulocyte colony-stimulating factor receptor
Seq:
Struc: 		 
Seq:
Struc: 		837 a.a.
208 a.a.
Protein chains
Pfam   ArchSchema ?
P09919  (CSF3_HUMAN) -  Granulocyte colony-stimulating factor
Seq:
Struc: 		207 a.a.
165 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     immune response   5 terms 
  Biochemical function     enzyme binding     4 terms  

 

 
DOI no: 10.1038/44394 Nature 401:713-717 (1999)
PubMed id: 10537111  
 
 
Atomic structure of the GCSF-receptor complex showing a new cytokine-receptor recognition scheme.
M.Aritomi, N.Kunishima, T.Okamoto, R.Kuroki, Y.Ota, K.Morikawa.
 
  ABSTRACT  
 
Granulocyte colony-stimulating factor (GCSF) is the principal growth factor regulating the maturation, proliferation and differentiation of the precursor cells of neutrophilic granulocytes and is used to treat neutropenia. GCSF is a member of the long-chain subtype of the class 1 cytokine superfamily, which includes growth hormone, erythropoietin, interleukin 6 and oncostatin M. Here we have determined the crystal structure of GCSF complexed to the BN-BC domains, the principal ligand-binding region of the GCSF receptor (GCSFR). The two receptor domains form a complex in a 2:2 ratio with the ligand, with a non-crystallographic pseudo-twofold axis through primarily the interdomain region and secondarily the BC domain. This structural view of a gp130-type receptor-ligand complex presents a new molecular basis for cytokine-receptor recognition.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 The GCSF-gs-CRH complex. MOL1 and MOL2 are shown in dark and light colours, respectively. a, Schematic drawing of the domain arrangements of GCSFR. The four highly conserved cysteines forming two disulphide bridges and the WSXWS motif in gs-CRH are indicated by double thin vertical and single thick vertical lines, respectively. b, c, Orthogonal views of the 2:2 complex. d, One 1:1 complex (MOL2) viewed from the right side of b and rotated 45° clockwise. The major (red) and minor contact (dark blue) regions, the WSXWS motif (yellow), the four conserved cysteines (yellow) and the sugar moiety (green) are depicted. e, Drawing of the GCSF-gs-CRH complex with the b and c perspectives denoted. f, Drawing of the major interfaces of MOL1 and MOL2, showing the principal hydrogen-bonding linkages between GCSF and the BN domain of gs-CRH. Ig-like, immunoglobulin-like; N-ter, N terminus. 		Figure 3.
Figure 3 Structural comparison of the GCSF-gs-CRH complex and ligand-free gp130. Stereoview of the MOL2 GCSF-gs-CRH complex (pink and light blue) and gp130 (green) after an alignment of the corresponding C atoms in the C-terminal domains of the receptors. The residues corresponding to the WSXWS motif and to Leu 290-Pro 291 in MOL2 are coloured yellow and red, respectively. The L strand in gp130 is coloured dark blue.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1999, 401, 713-717) copyright 1999.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19139076 C.Liongue, C.J.Hall, B.A.O'Connell, P.Crosier, and A.C.Ward (2009).
Zebrafish granulocyte colony-stimulating factor receptor signaling promotes myelopoiesis and myeloid cell migration.
  Blood, 113, 2535-2546.  
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.  
18400509 A.D.Panopoulos, and S.S.Watowich (2008).
Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and 'emergency' hematopoiesis.
  Cytokine, 42, 277-288.  
17947230 S.K.Olsen, N.Ota, S.Kishishita, M.Kukimoto-Niino, K.Murayama, H.Uchiyama, M.Toyama, T.Terada, M.Shirouzu, O.Kanagawa, and S.Yokoyama (2007).
Crystal Structure of the Interleukin-15{middle dot}Interleukin-15 Receptor {alpha} Complex: INSIGHTS INTO TRANS AND CIS PRESENTATION.
  J Biol Chem, 282, 37191-37204.
PDB code: 2psm
16540470 F.Peelman, H.Iserentant, A.S.De Smet, J.Vandekerckhove, L.Zabeau, and J.Tavernier (2006).
Mapping of binding site III in the leptin receptor and modeling of a hexameric leptin.leptin receptor complex.
  J Biol Chem, 281, 15496-15504.  
16492764 T.Tamada, E.Honjo, Y.Maeda, T.Okamoto, M.Ishibashi, M.Tokunaga, and R.Kuroki (2006).
Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex.
  Proc Natl Acad Sci U S A, 103, 3135-3140.
PDB code: 2d9q
  16511159 E.Honjo, T.Tamada, Y.Maeda, T.Koshiba, Y.Matsukura, T.Okamoto, M.Ishibashi, M.Tokunaga, and R.Kuroki (2005).
Crystallization of a 2:2 complex of granulocyte-colony stimulating factor (GCSF) with the ligand-binding region of the GCSF receptor.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 788-790.  
15933731 H.M.Hermanns, G.Müller-Newen, P.C.Heinrich, and S.Haan (2005).
Bow to your partner for signaling.
  Nat Struct Mol Biol, 12, 476-478.  
15870068 K.Arima, K.Sato, G.Tanaka, S.Kanaji, T.Terada, E.Honjo, R.Kuroki, Y.Matsuo, and K.Izuhara (2005).
Characterization of the interaction between interleukin-13 and interleukin-13 receptors.
  J Biol Chem, 280, 24915-24922.  
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.  
16131655 S.W.Raso, J.Abel, J.M.Barnes, K.M.Maloney, G.Pipes, M.J.Treuheit, J.King, and D.N.Brems (2005).
Aggregation of granulocyte-colony stimulating factor in vitro involves a conformationally altered monomeric state.
  Protein Sci, 14, 2246-2257.  
15213225 F.Peelman, K.Van Beneden, L.Zabeau, H.Iserentant, P.Ulrichts, D.Defeau, A.Verhee, D.Catteeuw, D.Elewaut, and J.Tavernier (2004).
Mapping of the leptin binding sites and design of a leptin antagonist.
  J Biol Chem, 279, 41038-41046.  
12734179 C.Couturier, and R.Jockers (2003).
Activation of the leptin receptor by a ligand-induced conformational change of constitutive receptor dimers.
  J Biol Chem, 278, 26604-26611.  
  14512227 J.R.Desjarlais, and G.A.Lazar (2003).
Negative design for improved therapeutic proteins.
  Trends Biotechnol, 21, 425-427.  
12524421 M.L.Doyle, S.S.Tian, S.G.Miller, L.Kessler, A.E.Baker, M.R.Brigham-Burke, S.B.Dillon, K.J.Duffy, R.M.Keenan, R.Lehr, J.Rosen, L.A.Schneeweis, J.Trill, P.R.Young, J.I.Luengo, and P.Lamb (2003).
Selective binding and oligomerization of the murine granulocyte colony-stimulating factor receptor by a low molecular weight, nonpeptidyl ligand.
  J Biol Chem, 278, 9426-9434.  
12791136 M.P.Machner, S.Frese, W.D.Schubert, V.Orian-Rousseau, E.Gherardi, J.Wehland, H.H.Niemann, and D.W.Heinz (2003).
Aromatic amino acids at the surface of InlB are essential for host cell invasion by Listeria monocytogenes.
  Mol Microbiol, 48, 1525-1536.  
12717025 M.S.Ricci, C.A.Sarkar, E.M.Fallon, D.A.Lauffenburger, and D.N.Brems (2003).
pH Dependence of structural stability of interleukin-2 and granulocyte colony-stimulating factor.
  Protein Sci, 12, 1030-1038.  
12237471 D.N.Brems (2002).
The kinetics of G-CSF folding.
  Protein Sci, 11, 2504-2511.  
12297050 H.Ogiso, R.Ishitani, O.Nureki, S.Fukai, M.Yamanaka, J.H.Kim, K.Saito, A.Sakamoto, M.Inoue, M.Shirouzu, and S.Yokoyama (2002).
Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains.
  Cell, 110, 775-787.
PDB code: 1ivo
12440146 K.Morikawa (2002).
[Ligand recognition mechanism of G-CSF receptor and metabotropic glutamate receptor]
  Yakugaku Zasshi, 122, 855-868.  
11967378 P.Luo, R.J.Hayes, C.Chan, D.M.Stark, M.Y.Hwang, J.M.Jacinto, P.Juvvadi, H.S.Chung, A.Kundu, M.L.Ary, and B.I.Dahiyat (2002).
Development of a cytokine analog with enhanced stability using computational ultrahigh throughput screening.
  Protein Sci, 11, 1218-1226.  
12297049 T.P.Garrett, N.M.McKern, M.Lou, T.C.Elleman, T.E.Adams, G.O.Lovrecz, H.J.Zhu, F.Walker, M.J.Frenkel, P.A.Hoyne, R.N.Jorissen, E.C.Nice, A.W.Burgess, and C.W.Ward (2002).
Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha.
  Cell, 110, 763-773.
PDB code: 1mox
11747625 L.Runkel, C.De Dios, M.Karpusas, D.Baker, Z.Li, M.Zafari, M.Betzenhauser, C.Muldowney, S.Miller, P.N.Redlich, S.E.Grossberg, A.Whitty, and P.S.Hochman (2001).
Mapping of IFN-beta epitopes important for receptor binding and biologic activation: comparison of results achieved using antibody-based methods and alanine substitution mutagenesis.
  J Interferon Cytokine Res, 21, 931-941.  
11207369 P.D.Carr, S.E.Gustin, A.P.Church, J.M.Murphy, S.C.Ford, D.A.Mann, D.M.Woltring, I.Walker, D.L.Ollis, and I.G.Young (2001).
Structure of the complete extracellular domain of the common beta subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel dimer configuration.
  Cell, 104, 291-300.
PDB code: 1gh7
10899108 C.Yoon, S.C.Johnston, J.Tang, M.Stahl, J.F.Tobin, and W.S.Somers (2000).
Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12.
  EMBO J, 19, 3530-3541.
PDB codes: 1f42 1f45
10618369 D.J.Stauber, A.D.DiGabriele, and W.A.Hendrickson (2000).
Structural interactions of fibroblast growth factor receptor with its ligands.
  Proc Natl Acad Sci U S A, 97, 49-54.
PDB code: 1djs
10835339 J.Bravo, and J.K.Heath (2000).
Receptor recognition by gp130 cytokines.
  EMBO J, 19, 2399-2411.  
10818353 M.Aritomi, N.Kunishima, N.Okitsu, M.Shimizu, Y.Ota, and K.Morikawa (2000).
Purification, crystallization and preliminary X-ray analysis of a complex between granulocyte colony-stimulating factor and its soluble receptor.
  Acta Crystallogr D Biol Crystallogr, 56, 751-753.  
10753817 M.C.Deller, and E.Yvonne Jones (2000).
Cell surface receptors.
  Curr Opin Struct Biol, 10, 213-219.  
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.