Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation

Science

Volumn 283, Issue 5404, 1999, Pages 987-990

  Livnah, Oded ^a,c   Stura, Enrico A ^a,d   Middleton, Steven A ^b   Johnson, Dana L ^b   Jolliffe, Linda K ^b   Wilson, Ian A ^b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b Drug Discovery Raritan   (United States)

^c HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^d CEA SACLAY   (France)

Author keywords

[No Author keywords available]

Indexed keywords

CELL SURFACE RECEPTOR; ERYTHROPOIETIN RECEPTOR;

ARTICLE; BINDING SITE; CELL SURFACE; CRYSTAL STRUCTURE; DIMERIZATION; LIGAND BINDING; MODEL; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN PHOSPHORYLATION; RECEPTOR BINDING; SIGNAL TRANSDUCTION; STRUCTURE ANALYSIS;

CELL MEMBRANE; CRYSTALLOGRAPHY, X-RAY; DIMERIZATION; ERYTHROPOIETIN; HUMANS; HYDROGEN BONDING; JANUS KINASE 2; LIGANDS; MODELS, MOLECULAR; PEPTIDE FRAGMENTS; PEPTIDES, CYCLIC; PROTEIN CONFORMATION; PROTEIN-TYROSINE KINASES; PROTO-ONCOGENE PROTEINS; RECEPTORS, ERYTHROPOIETIN;

EID: 0033548259     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.283.5404.987     Document Type: Article

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56. Crystallographic programs and methods. DENZO and SCALEPACK: Z. Otwinowski and W. Minor, Methods Enzymol. 276, 307 (1997); AMoRE: J. Navaza, Acta Crystallgr. A50, 157 (1994); CCP4: S. Bailey, ibid., p. 760; X-PLOR: A. T. Brünger, ibid. A47, 195 (1991); A. T. Brünger, X-PLOR. Version 3.1: A system for x-ray and NMR (Yale Univ. Press, New Haven, CT 1992); bulk solvent: J. S. Jiang and A. T. Brünger, J. Mol. Biol. 243, 100 (1994); Program O: T. A. Jones, J. Y. Zou, S. W. Cowan, M. Kjeldgaard, Acta Crystallogr. A47, 110 (1991); PROCHECK: R. A. Laskowski, M. W. MacArthur, D. S. Moss, J. M. Thornton, J. Appl. Crystallogr. 26, 283 (1993); GRASP: A. Nicholls, R. Bharadwaj, B. Honig, Biophys. J. 64, 166 (1993).
57. Crystallographic programs and methods. DENZO and SCALEPACK: Z. Otwinowski and W. Minor, Methods Enzymol. 276, 307 (1997); AMoRE: J. Navaza, Acta Crystallgr. A50, 157 (1994); CCP4: S. Bailey, ibid., p. 760; X-PLOR: A. T. Brünger, ibid. A47, 195 (1991); A. T. Brünger, X-PLOR. Version 3.1: A system for x-ray and NMR (Yale Univ. Press, New Haven, CT 1992); bulk solvent: J. S. Jiang and A. T. Brünger, J. Mol. Biol. 243, 100 (1994); Program O: T. A. Jones, J. Y. Zou, S. W. Cowan, M. Kjeldgaard, Acta Crystallogr. A47, 110 (1991); PROCHECK: R. A. Laskowski, M. W. MacArthur, D. S. Moss, J. M. Thornton, J. Appl. Crystallogr. 26, 283 (1993); GRASP: A. Nicholls, R. Bharadwaj, B. Honig, Biophys. J. 64, 166 (1993).
58. Crystallographic programs and methods. DENZO and SCALEPACK: Z. Otwinowski and W. Minor, Methods Enzymol. 276, 307 (1997); AMoRE: J. Navaza, Acta Crystallgr. A50, 157 (1994); CCP4: S. Bailey, ibid., p. 760; X-PLOR: A. T. Brünger, ibid. A47, 195 (1991); A. T. Brünger, X-PLOR. Version 3.1: A system for x-ray and NMR (Yale Univ. Press, New Haven, CT 1992); bulk solvent: J. S. Jiang and A. T. Brünger, J. Mol. Biol. 243, 100 (1994); Program O: T. A. Jones, J. Y. Zou, S. W. Cowan, M. Kjeldgaard, Acta Crystallogr. A47, 110 (1991); PROCHECK: R. A. Laskowski, M. W. MacArthur, D. S. Moss, J. M. Thornton, J. Appl. Crystallogr. 26, 283 (1993); GRASP: A. Nicholls, R. Bharadwaj, B. Honig, Biophys. J. 64, 166 (1993).
59. Crystallographic programs and methods. DENZO and SCALEPACK: Z. Otwinowski and W. Minor, Methods Enzymol. 276, 307 (1997); AMoRE: J. Navaza, Acta Crystallgr. A50, 157 (1994); CCP4: S. Bailey, ibid., p. 760; X-PLOR: A. T. Brünger, ibid. A47, 195 (1991); A. T. Brünger, X-PLOR. Version 3.1: A system for x-ray and NMR (Yale Univ. Press, New Haven, CT 1992); bulk solvent: J. S. Jiang and A. T. Brünger, J. Mol. Biol. 243, 100 (1994); Program O: T. A. Jones, J. Y. Zou, S. W. Cowan, M. Kjeldgaard, Acta Crystallogr. A47, 110 (1991); PROCHECK: R. A. Laskowski, M. W. MacArthur, D. S. Moss, J. M. Thornton, J. Appl. Crystallogr. 26, 283 (1993); GRASP: A. Nicholls, R. Bharadwaj, B. Honig, Biophys. J. 64, 166 (1993).
60. Crystallographic programs and methods. DENZO and SCALEPACK: Z. Otwinowski and W. Minor, Methods Enzymol. 276, 307 (1997); AMoRE: J. Navaza, Acta Crystallgr. A50, 157 (1994); CCP4: S. Bailey, ibid., p. 760; X-PLOR: A. T. Brünger, ibid. A47, 195 (1991); A. T. Brünger, X-PLOR. Version 3.1: A system for x-ray and NMR (Yale Univ. Press, New Haven, CT 1992); bulk solvent: J. S. Jiang and A. T. Brünger, J. Mol. Biol. 243, 100 (1994); Program O: T. A. Jones, J. Y. Zou, S. W. Cowan, M. Kjeldgaard, Acta Crystallogr. A47, 110 (1991); PROCHECK: R. A. Laskowski, M. W. MacArthur, D. S. Moss, J. M. Thornton, J. Appl. Crystallogr. 26, 283 (1993); GRASP: A. Nicholls, R. Bharadwaj, B. Honig, Biophys. J. 64, 166 (1993).
61. Crystallographic programs and methods. DENZO and SCALEPACK: Z. Otwinowski and W. Minor, Methods Enzymol. 276, 307 (1997); AMoRE: J. Navaza, Acta Crystallgr. A50, 157 (1994); CCP4: S. Bailey, ibid., p. 760; X-PLOR: A. T. Brünger, ibid. A47, 195 (1991); A. T. Brünger, X-PLOR. Version 3.1: A system for x-ray and NMR (Yale Univ. Press, New Haven, CT 1992); bulk solvent: J. S. Jiang and A. T. Brünger, J. Mol. Biol. 243, 100 (1994); Program O: T. A. Jones, J. Y. Zou, S. W. Cowan, M. Kjeldgaard, Acta Crystallogr. A47, 110 (1991); PROCHECK: R. A. Laskowski, M. W. MacArthur, D. S. Moss, J. M. Thornton, J. Appl. Crystallogr. 26, 283 (1993); GRASP: A. Nicholls, R. Bharadwaj, B. Honig, Biophys. J. 64, 166 (1993).
62. Crystallographic programs and methods. DENZO and SCALEPACK: Z. Otwinowski and W. Minor, Methods Enzymol. 276, 307 (1997); AMoRE: J. Navaza, Acta Crystallgr. A50, 157 (1994); CCP4: S. Bailey, ibid., p. 760; X-PLOR: A. T. Brünger, ibid. A47, 195 (1991); A. T. Brünger, X-PLOR. Version 3.1: A system for x-ray and NMR (Yale Univ. Press, New Haven, CT 1992); bulk solvent: J. S. Jiang and A. T. Brünger, J. Mol. Biol. 243, 100 (1994); Program O: T. A. Jones, J. Y. Zou, S. W. Cowan, M. Kjeldgaard, Acta Crystallogr. A47, 110 (1991); PROCHECK: R. A. Laskowski, M. W. MacArthur, D. S. Moss, J. M. Thornton, J. Appl. Crystallogr. 26, 283 (1993); GRASP: A. Nicholls, R. Bharadwaj, B. Honig, Biophys. J. 64, 166 (1993).
63. Crystallographic programs and methods. DENZO and SCALEPACK: Z. Otwinowski and W. Minor, Methods Enzymol. 276, 307 (1997); AMoRE: J. Navaza, Acta Crystallgr. A50, 157 (1994); CCP4: S. Bailey, ibid., p. 760; X-PLOR: A. T. Brünger, ibid. A47, 195 (1991); A. T. Brünger, X-PLOR. Version 3.1: A system for x-ray and NMR (Yale Univ. Press, New Haven, CT 1992); bulk solvent: J. S. Jiang and A. T. Brünger, J. Mol. Biol. 243, 100 (1994); Program O: T. A. Jones, J. Y. Zou, S. W. Cowan, M. Kjeldgaard, Acta Crystallogr. A47, 110 (1991); PROCHECK: R. A. Laskowski, M. W. MacArthur, D. S. Moss, J. M. Thornton, J. Appl. Crystallogr. 26, 283 (1993); GRASP: A. Nicholls, R. Bharadwaj, B. Honig, Biophys. J. 64, 166 (1993).
64. sym = ΣΣ|li - (l)|/Σli, where (l) is the average of equivalent reflections and the sum is extended over all measured observations for all unique reflections.
65. We thank J. Gately Luz for preparation of schematics in Fig. 1, K. Hotta for help with figures, S. Michnick and J. Kelly for helpful discussions, and R. Syed and R. Stroud for providing data for Fig. 2C Supported in part by NIH grant GM49497 (I.A.W.) and the Rueff-Wormser Scholarship Fund (O.L). This is publication 11901-MB from The Scripps Research Institute. The unliganded EBP coordinates have been deposited in the Protein Data Bank (PDB) with the accession code 1em.