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PDBsum entry 1cn4

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protein Protein-protein interface(s) links
Haematopoietic cytokine PDB id
1cn4
Jmol
Contents
Protein chains
217 a.a. *
154 a.a. *
Waters ×15
* Residue conservation analysis
PDB id:
1cn4
Name: Haematopoietic cytokine
Title: Erythropoietin complexed with extracellular domains of erythropoietin receptor
Structure: Protein (erythropoietin receptor). Chain: a, b. Fragment: extracellular ligand binding domains. Engineered: yes. Mutation: yes. Protein (erythropoietin). Chain: c. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: pichia pastoris. Expression_system_taxid: 4922. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Homo-Dimer (from PDB file)
Resolution:
2.80Å     R-factor:   0.280     R-free:   0.336
Authors: R.M.Stroud,S.W.Reid
Key ref:
R.S.Syed et al. (1998). Efficiency of signalling through cytokine receptors depends critically on receptor orientation. Nature, 395, 511-516. PubMed id: 9774108 DOI: 10.1038/26773
Date:
25-May-99     Release date:   11-Aug-99    
Supersedes: 1blw
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P19235  (EPOR_HUMAN) -  Erythropoietin receptor
Seq:
Struc:
508 a.a.
217 a.a.*
Protein chain
Pfam   ArchSchema ?
P01588  (EPO_HUMAN) -  Erythropoietin
Seq:
Struc:
193 a.a.
154 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   5 terms 
  Biological process     regulation of transcription from RNA polymerase II promoter in response to hypoxia   37 terms 
  Biochemical function     protein binding     6 terms  

 

 
DOI no: 10.1038/26773 Nature 395:511-516 (1998)
PubMed id: 9774108  
 
 
Efficiency of signalling through cytokine receptors depends critically on receptor orientation.
R.S.Syed, S.W.Reid, C.Li, J.C.Cheetham, K.H.Aoki, B.Liu, H.Zhan, T.D.Osslund, A.J.Chirino, J.Zhang, J.Finer-Moore, S.Elliott, K.Sitney, B.A.Katz, D.J.Matthews, J.J.Wendoloski, J.Egrie, R.M.Stroud.
 
  ABSTRACT  
 
Human erythropoietin is a haematopoietic cytokine required for the differentiation and proliferation of precursor cells into red blood cells. It activates cells by binding and orientating two cell-surface erythropoietin receptors (EPORs) which trigger an intracellular phosphorylation cascade. The half-maximal response in a cellular proliferation assay is evoked at an erythropoietin concentration of 10 pM, 10(-2) of its Kd value for erythropoietin-EPOR binding site 1 (Kd approximately equal to nM), and 10(-5) of the Kd for erythropoietin-EPOR binding site 2 (Kd approximately equal to 1 microM). Overall half-maximal binding (IC50) of cell-surface receptors is produced with approximately 0.18 nM erythropoietin, indicating that only approximately 6% of the receptors would be bound in the presence of 10 pM erythropoietin. Other effective erythropoietin-mimetic ligands that dimerize receptors can evoke the same cellular responses but much less efficiently, requiring concentrations close to their Kd values (approximately 0.1 microM). The crystal structure of erythropoietin complexed to the extracellular ligand-binding domains of the erythropoietin receptor, determined at 1.9 A from two crystal forms, shows that erythropoietin imposes a unique 120 degrees angular relationship and orientation that is responsible for optimal signalling through intracellular kinase pathways.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Crystal structure of the erythropoietin-(EPObp)[2] complex. -Helices are shown as red cylinders and -sheets as green ribbons. Erythropoietin: A(8-26) up, B'(47-52), B(55-83) up, C(90-112) down, C'(114-121), D(138-161) down, 1(39-41), 2(133-135). Disulphide bridges: Cys 7-Cys 161, Cys 29-Cys 33. D1 domain of EPObp: 1(9-22), A(26-30), B(36-42), C(52-59), C'(65-68), D(69-74), E(78-85), F(95-103), G(106-113). Disulphide bridges: Cys 28-Cys 38, Cys 67-Cys 83. D2 domains of EPObp: A(119-132), B(137-143), C(154-162), C'(170-174), E(179-183), F(190-201), G(216-220). EPObp loops that interact with erythropoietin are labelled L1(31-35), L2(60-64), L3(86-94), L4(114-118), L5(144-153) and L6(202-205). The locations of residues in the WSXWS box, dimerizing mutation site^23 R130C, two Asn arrow Gln mutation sites (52, 164) on EPObp, and three Asn arrow Lys mutations (24, 38, 83) on erythropoietin are depicted as white spheres. EPO, erythropoietin.
Figure 2.
Figure 2 Stereo views. a, erythropoietin-(EPObp)[2]. b, (EMP1-EBP)[2]. c, hGH-(hGHbp)[2]. All the receptors are coloured blue, with their ligands in red. The intermolecular contacts (<4.5 ) involving receptor amino acids are shown in yellow; ligand amino acids with the receptor on the right-hand side (site 1 for erythropoietin and hGH) are shown in green; and ligand amino acids with the receptor on the left-hand side (site 2 for erythropoietin and hGH) are shown in white. Receptor orientations are also represented schematically at the right, with the horizontal membrane plane shown in grey and the corresponding vertical plane drawn in a chequered pattern.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1998, 395, 511-516) copyright 1998.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21421996 P.Colella, C.Iodice, U.Di Vicino, I.Annunziata, E.M.Surace, and A.Auricchio (2011).
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21058397 S.Indu, V.Kochat, S.Thakurela, C.Ramakrishnan, and R.Varadarajan (2011).
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20188141 N.E.Fox, J.Lim, R.Chen, and A.E.Geddis (2010).
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20223923 S.Guihard, D.Clay, L.Cocault, N.Saulnier, P.Opolon, M.Souyri, G.Pagès, J.Pouysségur, F.Porteu, and M.Gaudry (2010).
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20462497 S.I.Yoon, B.C.Jones, N.J.Logsdon, B.D.Harris, A.Deshpande, S.Radaeva, B.A.Halloran, B.Gao, and M.R.Walter (2010).
Structure and mechanism of receptor sharing by the IL-10R2 common chain.
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PDB code: 3lqm
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PEGylation markedly enhances the in vivo potency of recombinant human non-glycosylated erythropoietin: a comparison with glycosylated erythropoietin.
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Survival and proliferative roles of erythropoietin beyond the erythroid lineage.
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17936496 H.M.Rogers, X.Yu, J.Wen, R.Smith, E.Fibach, and C.T.Noguchi (2008).
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PDB codes: 2o6c 2o6d 2o6e 2o6f
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Nonnatural protein-protein interaction-pair design by key residues grafting.
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Erythropoietin after a century of research: younger than ever.
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Understanding mechanisms of gamma-globin gene regulation to develop strategies for pharmacological fetal hemoglobin induction.
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Wiggle-predicting functionally flexible regions from primary sequence.
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Evidence for ligand-independent multimerization of the IL-17 receptor.
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16557636 L.L.Kiessling, J.E.Gestwicki, and L.E.Strong (2006).
Synthetic multivalent ligands as probes of signal transduction.
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16332976 M.P.Menon, J.Fang, and D.M.Wojchowski (2006).
Core erythropoietin receptor signals for late erythroblast development.
  Blood, 107, 2662-2672.  
16414957 X.Lu, A.W.Gross, and H.F.Lodish (2006).
Active conformation of the erythropoietin receptor: random and cysteine-scanning mutagenesis of the extracellular juxtamembrane and transmembrane domains.
  J Biol Chem, 281, 7002-7011.  
15757425 D.H.Henry (2005).
Epoetin alfa for the treatment of cancer- and chemotherapy-related anaemia: product review and update.
  Expert Opin Pharmacother, 6, 295-310.  
15895091 G.Skiniotis, M.J.Boulanger, K.C.Garcia, and T.Walz (2005).
Signaling conformations of the tall cytokine receptor gp130 when in complex with IL-6 and IL-6 receptor.
  Nat Struct Mol Biol, 12, 545-551.  
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.
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15657048 K.F.Kubatzky, W.Liu, K.Goldgraben, C.Simmerling, S.O.Smith, and S.N.Constantinescu (2005).
Structural requirements of the extracellular to transmembrane domain junction for erythropoietin receptor function.
  J Biol Chem, 280, 14844-14854.  
19003054 M.Nagao, T.C.Wen, M.Okamoto, K.Irie, T.Takaku, and M.Sakanaka (2005).
In vivo Neuroprotective Activity of Epopeptide AB Against Ischemic Damage.
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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.  
15826943 T.Ishino, C.Urbina, M.Bhattacharya, D.Panarello, and I.Chaiken (2005).
Receptor epitope usage by an interleukin-5 mimetic peptide.
  J Biol Chem, 280, 22951-22961.  
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
15117952 H.Ogawa, Y.Qiu, C.M.Ogata, and K.S.Misono (2004).
Crystal structure of hormone-bound atrial natriuretic peptide receptor extracellular domain: rotation mechanism for transmembrane signal transduction.
  J Biol Chem, 279, 28625-28631.
PDB code: 1t34
15060062 J.M.Murphy, S.C.Ford, J.E.Olsen, S.E.Gustin, P.D.Jeffrey, D.L.Ollis, and I.G.Young (2004).
Interleukin-3 binding to the murine betaIL-3 and human betac receptors involves functional epitopes formed by domains 1 and 4 of different protein chains.
  J Biol Chem, 279, 26500-26508.  
14769915 M.D.Feese, T.Tamada, Y.Kato, Y.Maeda, M.Hirose, Y.Matsukura, H.Shigematsu, T.Muto, A.Matsumoto, H.Watarai, K.Ogami, T.Tahara, T.Kato, H.Miyazaki, and R.Kuroki (2004).
Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment.
  Proc Natl Acad Sci U S A, 101, 1816-1821.
PDB codes: 1v7m 1v7n
14757769 S.Elliott, D.Chang, E.Delorme, T.Eris, and T.Lorenzini (2004).
Structural requirements for additional N-linked carbohydrate on recombinant human erythropoietin.
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15064755 S.Keller, J.Nickel, J.L.Zhang, W.Sebald, and T.D.Mueller (2004).
Molecular recognition of BMP-2 and BMP receptor IA.
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PDB codes: 1reu 1rew
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The high- and low-affinity receptor binding sites of growth hormone are allosterically coupled.
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15468961 W.Jelkmann (2004).
Molecular biology of erythropoietin.
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15322761 W.Jelkmann, and K.Wagner (2004).
Beneficial and ominous aspects of the pleiotropic action of erythropoietin.
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15449706 W.Sebald, J.Nickel, J.L.Zhang, and T.D.Mueller (2004).
Molecular recognition in bone morphogenetic protein (BMP)/receptor interaction.
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14679212 X.Cheng, M.Kinosaki, M.Takami, Y.Choi, H.Zhang, and R.Murali (2004).
Disabling of receptor activator of nuclear factor-kappaB (RANK) receptor complex by novel osteoprotegerin-like peptidomimetics restores bone loss in vivo.
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Natriuretic peptide receptor A activation stabilizes a membrane-distal dimer interface.
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Structural basis for tetrodotoxin-resistant sodium channel binding by mu-conotoxin SmIIIA.
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PDB code: 1q2j
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Hematopoietic cell survival signals are elicited through non-tyrosine-containing sequences in the membrane-proximal region of the erythropoietin receptor (EPOR) by a Stat5-dependent pathway.
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12667445 J.Greenwald, J.Groppe, P.Gray, E.Wiater, W.Kwiatkowski, W.Vale, and S.Choe (2003).
The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly.
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PDB codes: 1lx5 1lxi
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A novel functional epitope formed by domains 1 and 4 of the human common beta-subunit is involved in receptor activation by granulocyte macrophage colony-stimulating factor and interleukin 5.
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Atomic contact vectors in protein-protein recognition.
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12655020 M.Kawahara, H.Ueda, S.Morita, K.Tsumoto, I.Kumagai, and T.Nagamune (2003).
Bypassing antibiotic selection: positive screening of genetically modified cells with an antigen-dependent proliferation switch.
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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.  
14636581 N.Seubert, Y.Royer, J.Staerk, K.F.Kubatzky, V.Moucadel, S.Krishnakumar, S.O.Smith, and S.N.Constantinescu (2003).
Active and inactive orientations of the transmembrane and cytosolic domains of the erythropoietin receptor dimer.
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12930840 S.N.Constantinescu, T.Keren, W.P.Russ, I.Ubarretxena-Belandia, Y.Malka, K.F.Kubatzky, D.M.Engelman, H.F.Lodish, and Y.I.Henis (2003).
The erythropoietin receptor transmembrane domain mediates complex formation with viral anemic and polycythemic gp55 proteins.
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12930995 S.T.Walsh, L.M.Jevitts, J.E.Sylvester, and A.A.Kossiakoff (2003).
Site2 binding energetics of the regulatory step of growth hormone-induced receptor homodimerization.
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12660162 T.B.Thompson, T.K.Woodruff, and T.S.Jardetzky (2003).
Structures of an ActRIIB:activin A complex reveal a novel binding mode for TGF-beta ligand:receptor interactions.
  EMBO J, 22, 1555-1566.
PDB codes: 1nys 1nyu
12676936 T.Rose, J.L.Moreau, R.Eckenberg, and J.Thèze (2003).
Structural analysis and modeling of a synthetic interleukin-2 mimetic and its interleukin-2Rbeta2 receptor.
  J Biol Chem, 278, 22868-22876.  
12011054 A.Berezov, J.Chen, Q.Liu, H.T.Zhang, M.I.Greene, and R.Murali (2002).
Disabling receptor ensembles with rationally designed interface peptidomimetics.
  J Biol Chem, 277, 28330-28339.  
11750880 A.E.Geddis, H.M.Linden, and K.Kaushansky (2002).
Thrombopoietin: a pan-hematopoietic cytokine.
  Cytokine Growth Factor Rev, 13, 61-73.  
12110039 A.P.Maxwell (2002).
Novel erythropoiesis-stimulating protein in the management of the anemia of chronic renal failure.
  Kidney Int, 62, 720-729.  
12047380 A.Timmermann, A.Küster, I.Kurth, P.C.Heinrich, and G.Müller-Newen (2002).
A functional role of the membrane-proximal extracellular domains of the signal transducer gp130 in heterodimerization with the leukemia inhibitory factor receptor.
  Eur J Biochem, 269, 2716-2726.  
12093920 B.C.Jones, N.J.Logsdon, K.Josephson, J.Cook, P.A.Barry, and M.R.Walter (2002).
Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1.
  Proc Natl Acad Sci U S A, 99, 9404-9409.
PDB code: 1lqs
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
11966740 J.E.Rowland, N.J.Marshall, K.C.Leung, K.K.Ho, A.M.Cotterill, S.W.Rowlinson, and M.J.Waters (2002).
A novel bioassay for human somatogenic activity in serum samples supports the clinical reliability of immunoassays.
  Clin Endocrinol (Oxf), 56, 475-485.  
12121224 J.M.Ellery, and P.J.Nicholls (2002).
Possible mechanism for the alpha subunit of the interleukin-2 receptor (CD25) to influence interleukin-2 receptor signal transduction.
  Immunol Cell Biol, 80, 351-357.  
11750878 J.M.Ellery, and P.J.Nicholls (2002).
Alternate signalling pathways from the interleukin-2 receptor.
  Cytokine Growth Factor Rev, 13, 27-40.  
12011064 J.S.Greiser, C.Stross, P.C.Heinrich, I.Behrmann, and H.M.Hermanns (2002).
Orientational constraints of the gp130 intracellular juxtamembrane domain for signaling.
  J Biol Chem, 277, 26959-26965.  
12440146 K.Morikawa (2002).
[Ligand recognition mechanism of G-CSF receptor and metabotropic glutamate receptor]
  Yakugaku Zasshi, 122, 855-868.  
12221088 M.Graille, S.Harrison, M.P.Crump, S.C.Findlow, N.G.Housden, B.H.Muller, N.Battail-Poirot, G.Sibaï, B.J.Sutton, M.J.Taussig, C.Jolivet-Reynaud, M.G.Gore, and E.A.Stura (2002).
Evidence for plasticity and structural mimicry at the immunoglobulin light chain-protein L interface.
  J Biol Chem, 277, 47500-47506.
PDB code: 1mhh
11997394 R.Ketteler, A.C.Heinrich, J.K.Offe, V.Becker, J.Cohen, D.Neumann, and U.Klingmüller (2002).
A functional green fluorescent protein-erythropoietin receptor despite physical separation of JAK2 binding site and tyrosine residues.
  J Biol Chem, 277, 26547-26552.  
11976502 R.Kuroki, M.Hirose, Y.Kato, M.D.Feese, T.Tamada, H.Shigematsu, H.Watarai, Y.Maeda, T.Tahara, T.Kato, and H.Miyazaki (2002).
Crystallization of the functional domain of human thrombopoietin using an antigen-binding fragment derived from neutralizing monoclonal antibody.
  Acta Crystallogr D Biol Crystallogr, 58, 856-858.  
11345195 C.J.Bagley, J.M.Woodcock, M.A.Guthridge, F.C.Stomski, and A.F.Lopez (2001).
Structural and functional hot spots in cytokine receptors.
  Int J Hematol, 73, 299-307.  
11251288 D.Macmillan, R.M.Bill, K.A.Sage, D.Fern, and S.L.Flitsch (2001).
Selective in vitro glycosylation of recombinant proteins: semi-synthesis of novel homogeneous glycoforms of human erythropoietin.
  Chem Biol, 8, 133-145.  
11308268 J.C.Egrie, and J.K.Browne (2001).
Development and characterization of novel erythropoiesis stimulating protein (NESP).
  Br J Cancer, 84, 3.  
  11606572 J.L.Taupin, P.Legembre, J.Bitard, S.Daburon, V.Pitard, F.Blanchard, L.Duplomb, A.Godard, Y.Jacques, and J.F.Moreau (2001).
Identification of agonistic and antagonistic antibodies against gp190, the leukemia inhibitory factor receptor, reveals distinct roles for its two cytokine-binding domains.
  J Biol Chem, 276, 47975-47981.  
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.  
11250200 M.Randal, and A.A.Kossiakoff (2001).
The structure and activity of a monomeric interferon-gamma:alpha-chain receptor signaling complex.
  Structure, 9, 155-163.
PDB code: 1fyh
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
11358507 S.E.Gustin, A.P.Church, S.C.Ford, D.A.Mann, P.D.Carr, D.L.Ollis, and I.G.Young (2001).
Expression, crystallization and derivatization of the complete extracellular domain of the beta(c) subunit of the human IL-5, IL-3 and GM-CSF receptors.
  Eur J Biochem, 268, 2905-2911.  
11239466 S.N.Constantinescu, L.J.Huang, H.Nam, and H.F.Lodish (2001).
The erythropoietin receptor cytosolic juxtamembrane domain contains an essential, precisely oriented, hydrophobic motif.
  Mol Cell, 7, 377-385.  
11296286 S.N.Constantinescu, T.Keren, M.Socolovsky, H.Nam, Y.I.Henis, and H.F.Lodish (2001).
Ligand-independent oligomerization of cell-surface erythropoietin receptor is mediated by the transmembrane domain.
  Proc Natl Acad Sci U S A, 98, 4379-4384.  
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
10903952 E.J.Sundberg, and R.A.Mariuzza (2000).
Luxury accommodations: the expanding role of structural plasticity in protein-protein interactions.
  Structure, 8, R137-R142.  
11114500 E.Y.Jones (2000).
The tumour necrosis factor receptor family: life or death choices.
  Curr Opin Struct Biol, 10, 644-648.  
10671483 G.Müller-Newen, A.Küster, J.Wijdenes, F.Schaper, and P.C.Heinrich (2000).
Studies on the interleukin-6-type cytokine signal transducer gp130 reveal a novel mechanism of receptor activation by monoclonal antibodies.
  J Biol Chem, 275, 4579-4586.  
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.  
10997905 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.
  Structure, 8, 863-874.
PDB code: 1evs
10755612 M.Degano, K.C.Garcia, V.Apostolopoulos, M.G.Rudolph, L.Teyton, and I.A.Wilson (2000).
A functional hot spot for antigen recognition in a superagonist TCR/MHC complex.
  Immunity, 12, 251-261.
PDB code: 1g6r
11055378 R.Sasaki, S.Masuda, and M.Nagao (2000).
Erythropoietin: multiple physiological functions and regulation of biosynthesis.
  Biosci Biotechnol Biochem, 64, 1775-1793.  
11564570 S.G.Miller (2000).
Discovery of cytokine mimics using cell-based systems.
  Drug Discov Today, 5, 77-83.  
10637647 S.I.Taylor (2000).
Rational design of peptide agonists of cell-surface receptors.
  Trends Pharmacol Sci, 21, 9.  
10828073 S.N.Behncken, N.Billestrup, R.Brown, J.Amstrup, B.Conway-Campbell, and M.J.Waters (2000).
Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation.
  J Biol Chem, 275, 17000-17007.  
10933390 W.W.Schamel, and M.Reth (2000).
Monomeric and oligomeric complexes of the B cell antigen receptor.
  Immunity, 13, 5.  
10455149 A.J.Sytkowski, E.D.Lunn, M.A.Risinger, and K.L.Davis (1999).
An erythropoietin fusion protein comprised of identical repeating domains exhibits enhanced biological properties.
  J Biol Chem, 274, 24773-24778.  
10099129 A.Whitty, and C.W.Borysenko (1999).
Small molecule cytokine mimetics.
  Chem Biol, 6, R107-R118.  
10574803 C.Wiesmann, and A.M.de Vos (1999).
Putting two and two together: crystal structure of the FGF-receptor complex.
  Structure, 7, R251-R255.  
  10338012 D.K.Hendrix, T.E.Klein, I.D.Kuntz, and T.E.Klien (1999).
Macromolecular docking of a three-body system: the recognition of human growth hormone by its receptor.
  Protein Sci, 8, 1010-1022.  
10097129 G.A.Snyder, A.G.Brooks, and P.D.Sun (1999).
Crystal structure of the HLA-Cw3 allotype-specific killer cell inhibitory receptor KIR2DL2.
  Proc Natl Acad Sci U S A, 96, 3864-3869.
PDB codes: 2dl2 2dli
10469554 G.Jiang, and T.Hunter (1999).
Receptor signaling: when dimerization is not enough.
  Curr Biol, 9, R568-R571.  
10506179 H.J.Zhu, and A.M.Sizeland (1999).
Extracellular domain of the transforming growth factor-beta receptor negatively regulates ligand-independent receptor activation.
  J Biol Chem, 274, 29220-29227.  
10607675 I.A.Wilson, and L.K.Jolliffe (1999).
The structure, organization, activation and plasticity of the erythropoietin receptor.
  Curr Opin Struct Biol, 9, 696-704.  
9974393 I.Remy, I.A.Wilson, and S.W.Michnick (1999).
Erythropoietin receptor activation by a ligand-induced conformation change.
  Science, 283, 990-993.  
10494829 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.  
10610089 K.D.Wittrup (1999).
Phage on display.
  Trends Biotechnol, 17, 423-424.  
10547147 K.E.Mogensen, M.Lewerenz, J.Reboul, G.Lutfalla, and G.Uzé (1999).
The type I interferon receptor: structure, function, and evolution of a family business.
  J Interferon Cytokine Res, 19, 1069-1098.  
9974392 O.Livnah, E.A.Stura, S.A.Middleton, D.L.Johnson, L.K.Jolliffe, and I.A.Wilson (1999).
Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation.
  Science, 283, 987-990.
PDB code: 1ern
10318834 S.A.Middleton, F.P.Barbone, D.L.Johnson, R.L.Thurmond, Y.You, F.J.McMahon, R.Jin, O.Livnah, J.Tullai, F.X.Farrell, M.A.Goldsmith, I.A.Wilson, and L.K.Jolliffe (1999).
Shared and unique determinants of the erythropoietin (EPO) receptor are important for binding EPO and EPO mimetic peptide.
  J Biol Chem, 274, 14163-14169.  
10518592 S.A.Qureshi, R.M.Kim, Z.Konteatis, D.E.Biazzo, H.Motamedi, R.Rodrigues, J.A.Boice, J.R.Calaycay, M.A.Bednarek, P.Griffin, Y.D.Gao, K.Chapman, and D.F.Mark (1999).
Mimicry of erythropoietin by a nonpeptide molecule.
  Proc Natl Acad Sci U S A, 96, 12156-12161.  
11232332 S.M.McWhirter, S.S.Pullen, B.G.Werneburg, M.E.Labadia, R.H.Ingraham, J.J.Crute, M.R.Kehry, and T.Alber (1999).
Structural and biochemical analysis of signal transduction by the TRAF family of adapter proteins.
  Cold Spring Harb Symp Quant Biol, 64, 551-562.  
10411888 S.M.McWhirter, S.S.Pullen, J.M.Holton, J.J.Crute, M.R.Kehry, and T.Alber (1999).
Crystallographic analysis of CD40 recognition and signaling by human TRAF2.
  Proc Natl Acad Sci U S A, 96, 8408-8413.
PDB code: 1qsc
10611645 S.N.Behncken, and M.J.Waters (1999).
Molecular recognition events involved in the activation of the growth hormone receptor by growth hormone.
  J Mol Recognit, 12, 355-362.  
10369674 S.N.Constantinescu, X.Liu, W.Beyer, A.Fallon, S.Shekar, Y.I.Henis, S.O.Smith, and H.F.Lodish (1999).
Activation of the erythropoietin receptor by the gp55-P viral envelope protein is determined by a single amino acid in its transmembrane domain.
  EMBO J, 18, 3334-3347.  
10582340 S.S.Watowich (1999).
Activation of erythropoietin signaling by receptor dimerization.
  Int J Biochem Cell Biol, 31, 1075-1088.  
10219247 T.Hage, W.Sebald, and P.Reinemer (1999).
Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface.
  Cell, 97, 271-281.
PDB code: 1iar
10377456 T.Naranda, K.Wong, R.I.Kaufman, A.Goldstein, and L.Olsson (1999).
Activation of erythropoietin receptor in the absence of hormone by a peptide that binds to a domain different from the hormone binding site.
  Proc Natl Acad Sci U S A, 96, 7569-7574.  
9808034 M.D.Ballinger, and J.A.Wells (1998).
Will any dimer do?
  Nat Struct Biol, 5, 938-940.  
9808045 O.Livnah, D.L.Johnson, E.A.Stura, F.X.Farrell, F.P.Barbone, Y.You, K.D.Liu, M.A.Goldsmith, W.He, C.D.Krause, S.Pestka, L.K.Jolliffe, and I.A.Wilson (1998).
An antagonist peptide-EPO receptor complex suggests that receptor dimerization is not sufficient for activation.
  Nat Struct Biol, 5, 993.
PDB code: 1eba
9875849 S.C.Garman, J.P.Kinet, and T.S.Jardetzky (1998).
Crystal structure of the human high-affinity IgE receptor.
  Cell, 95, 951-961.
PDB code: 1f2q
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