Functional Mimicry of a Protein Hormone by a Peptide Agonist: The EPO Receptor Complex at 2.8 Å
10.1126/science.273.5274.464
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

The functional mimicry of a protein by an unrelated small molecule has been a formidable challenge. Now, however, the biological activity of a 166-residue hematopoietic growth hormone, erythropoietin (EPO), with its class 1 cytokine receptor has been mimicked by a 20-residue cyclic peptide unrelated in sequence to the natural ligand. The crystal structure at 2.8 Å resolution of a complex of this agonist peptide with the extracellular domain of EPO receptor reveals that a peptide dimer induces an almost perfect twofold dimerization of the receptor. The dimer assembly differs from that of the human growth hormone (hGH) receptor complex and suggests that more than one mode of dimerization may be able to induce signal transduction and cell proliferation. The EPO receptor binding site, defined by peptide interaction, corresponds to the smaller functional epitope identified for hGH receptor. Similarly, the EPO mimetic peptide ligand can be considered as a minimal hormone, and suggests the design of nonpeptidic small molecule mimetics for EPO and other cytokines may indeed be achievable.

Bibliography

Livnah, O., Stura, E. A., Johnson, D. L., Middleton, S. A., Mulcahy, L. S., Wrighton, N. C., Dower, W. J., Jolliffe, L. K., & Wilson, I. A. (1996). Functional Mimicry of a Protein Hormone by a Peptide Agonist: The EPO Receptor Complex at 2.8 Å. Science, 273(5274), 464–471.

Authors 9
  1. Oded Livnah (first)
  2. Enrico A. Stura (additional)
  3. Dana L. Johnson (additional)
  4. Steven A. Middleton (additional)
  5. Linda S. Mulcahy (additional)
  6. Nicholas C. Wrighton (additional)
  7. William J. Dower (additional)
  8. Linda K. Jolliffe (additional)
  9. Ian A. Wilson (additional)
References 69 Referenced 507
  1. ADZHUBEI A.A., LEFT-HANDED POLYPROLINE-II HELICES COMMONLY OCCUR IN GLOBULAR-PROTEINS, JOURNAL OF MOLECULAR BIOLOGY 229, 472 (1993). (10.1006/jmbi.1993.1047) / JOURNAL OF MOLECULAR BIOLOGY / LEFT-HANDED POLYPROLINE-II HELICES COMMONLY OCCUR IN GLOBULAR-PROTEINS by ADZHUBEI A.A. (1993)
  2. BASS S.H., A SYSTEMATIC MUTATIONAL ANALYSIS OF HORMONE-BINDING DETERMINANTS IN THE HUMAN GROWTH-HORMONE RECEPTOR, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 88, 4498 (1991). (10.1073/pnas.88.10.4498) / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA / A SYSTEMATIC MUTATIONAL ANALYSIS OF HORMONE-BINDING DETERMINANTS IN THE HUMAN GROWTH-HORMONE RECEPTOR by BASS S.H. (1991)
  3. BAUMGARTNER J.W., THE ROLE OF THE WSXWS EQUIVALENT MOTIF IN GROWTH-HORMONE RECEPTOR FUNCTION, JOURNAL OF BIOLOGICAL CHEMISTRY 269, 29094 (1994). (10.1016/S0021-9258(19)62017-X) / JOURNAL OF BIOLOGICAL CHEMISTRY / THE ROLE OF THE WSXWS EQUIVALENT MOTIF IN GROWTH-HORMONE RECEPTOR FUNCTION by BAUMGARTNER J.W. (1994)
  4. BAZAN J.F., STRUCTURAL DESIGN AND MOLECULAR EVOLUTION OF A CYTOKINE RECEPTOR SUPERFAMILY, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87, 6934 (1990). (10.1073/pnas.87.18.6934) / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA / STRUCTURAL DESIGN AND MOLECULAR EVOLUTION OF A CYTOKINE RECEPTOR SUPERFAMILY by BAZAN J.F. (1990)
  5. BERNSTEIN F.C., PROTEIN DATA BANK - COMPUTER-BASED ARCHIVAL FILE FOR MACROMOLECULAR STRUCTURES, ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 185, 584 (1978). (10.1016/0003-9861(78)90204-7) / ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS / PROTEIN DATA BANK - COMPUTER-BASED ARCHIVAL FILE FOR MACROMOLECULAR STRUCTURES by BERNSTEIN F.C. (1978)
  6. BOISSEL J.P., ERYTHROPOIETIN STRUCTURE-FUNCTION-RELATIONSHIPS - MUTANT PROTEINS THAT TEST A MODEL OF TERTIARY STRUCTURE, JOURNAL OF BIOLOGICAL CHEMISTRY 268, 15983 (1993). (10.1016/S0021-9258(18)82348-1) / JOURNAL OF BIOLOGICAL CHEMISTRY / ERYTHROPOIETIN STRUCTURE-FUNCTION-RELATIONSHIPS - MUTANT PROTEINS THAT TEST A MODEL OF TERTIARY STRUCTURE by BOISSEL J.P. (1993)
  7. BORK P, THE IMMUNOGLOBULIN FOLD - STRUCTURAL CLASSIFICATION, SEQUENCE PATTERNS AND COMMON CORE, JOURNAL OF MOLECULAR BIOLOGY 242, 309 (1994). (10.1016/S0022-2836(84)71582-8) / JOURNAL OF MOLECULAR BIOLOGY / THE IMMUNOGLOBULIN FOLD - STRUCTURAL CLASSIFICATION, SEQUENCE PATTERNS AND COMMON CORE by BORK P (1994)
  8. BRUNGER A.T., SLOW-COOLING PROTOCOLS FOR CRYSTALLOGRAPHIC REFINEMENT BY SIMULATED ANNEALING, ACTA CRYSTALLOGRAPHICA SECTION A 46, 585 (1990). (10.1107/S0108767390002355) / ACTA CRYSTALLOGRAPHICA SECTION A / SLOW-COOLING PROTOCOLS FOR CRYSTALLOGRAPHIC REFINEMENT BY SIMULATED ANNEALING by BRUNGER A.T. (1990)
  9. BRUNGER A.T., XPLOR VERSION 3 1 SY (1992). / XPLOR VERSION 3 1 SY by BRUNGER A.T. (1992)
  10. BURLEY S.K., WEAKLY POLAR INTERACTIONS IN PROTEINS, ADVANCES IN PROTEIN CHEMISTRY 39, 125 (1988). (10.1016/S0065-3233(08)60376-9) / ADVANCES IN PROTEIN CHEMISTRY / WEAKLY POLAR INTERACTIONS IN PROTEINS by BURLEY S.K. (1988)
  11. CHAN AWE, IDENTIFICATION, CLASSIFICATION, AND ANALYSIS OF BETA-BULGES IN PROTEINS, PROTEIN SCIENCE 2, 1574 (1993). (10.1002/pro.5560021004) / PROTEIN SCIENCE / IDENTIFICATION, CLASSIFICATION, AND ANALYSIS OF BETA-BULGES IN PROTEINS by CHAN AWE (1993)
  12. 10.1126/science.7529940
  13. 10.1107/S0021889883010985
  14. 10.1126/science.1948064
  15. DAVIES D.R., ANTIBODY-ANTIGEN COMPLEXES, ANNUAL REVIEW OF BIOCHEMISTRY 59, 439 (1990). (10.1146/annurev.bi.59.070190.002255) / ANNUAL REVIEW OF BIOCHEMISTRY / ANTIBODY-ANTIGEN COMPLEXES by DAVIES D.R. (1990)
  16. DEVOS A.M., HUMAN GROWTH-HORMONE AND EXTRACELLULAR DOMAIN OF ITS RECEPTOR - CRYSTAL-STRUCTURE OF THE COMPLEX, SCIENCE 255, 306 (1992). (10.1126/science.1549776) / SCIENCE / HUMAN GROWTH-HORMONE AND EXTRACELLULAR DOMAIN OF ITS RECEPTOR - CRYSTAL-STRUCTURE OF THE COMPLEX by DEVOS A.M. (1992)
  17. 10.1126/science.271.5246.163
  18. FLOCCO M.M., PLANAR STACKING INTERACTIONS OF ARGININE AND AROMATIC SIDE-CHAINS IN PROTEINS, JOURNAL OF MOLECULAR BIOLOGY 235, 709 (1994). (10.1006/jmbi.1994.1022) / JOURNAL OF MOLECULAR BIOLOGY / PLANAR STACKING INTERACTIONS OF ARGININE AND AROMATIC SIDE-CHAINS IN PROTEINS by FLOCCO M.M. (1994)
  19. FOA P, ERYTHROPOIETIN - CLINICAL-APPLICATIONS, ACTA HAEMATOLOGICA 86, 162 (1991). (10.1159/000204826) / ACTA HAEMATOLOGICA / ERYTHROPOIETIN - CLINICAL-APPLICATIONS by FOA P (1991)
  20. 10.1126/science.256.5064.1677
  21. FUREY W.J., AM CRYST ASS 40 ANN (1990). / AM CRYST ASS 40 ANN by FUREY W.J. (1990)
  22. GUSTCHINA A, A MODEL OF THE COMPLEX BETWEEN INTERLEUKIN-4 AND ITS RECEPTORS, PROTEINS-STRUCTURE FUNCTION AND GENETICS 21, 140 (1995). (10.1002/prot.340210208) / PROTEINS-STRUCTURE FUNCTION AND GENETICS / A MODEL OF THE COMPLEX BETWEEN INTERLEUKIN-4 AND ITS RECEPTORS by GUSTCHINA A (1995)
  23. HANSEN J.N., ANTIBIOTICS SYNTHESIZED BY POSTTRANSLATIONAL MODIFICATION, ANNUAL REVIEW OF MICROBIOLOGY 47, 535 (1993). (10.1146/annurev.mi.47.100193.002535) / ANNUAL REVIEW OF MICROBIOLOGY / ANTIBIOTICS SYNTHESIZED BY POSTTRANSLATIONAL MODIFICATION by HANSEN J.N. (1993)
  24. HARLOS K, CRYSTAL-STRUCTURE OF THE EXTRACELLULAR REGION OF HUMAN TISSUE FACTOR, NATURE 370, 662 (1994). (10.1038/370662a0) / NATURE / CRYSTAL-STRUCTURE OF THE EXTRACELLULAR REGION OF HUMAN TISSUE FACTOR by HARLOS K (1994)
  25. HELDIN C.H., DIMERIZATION OF CELL-SURFACE RECEPTORS IN SIGNAL-TRANSDUCTION, CELL 80, 213 (1995). (10.1016/0092-8674(95)90404-2) / CELL / DIMERIZATION OF CELL-SURFACE RECEPTORS IN SIGNAL-TRANSDUCTION by HELDIN C.H. (1995)
  26. HILTON D.J., Saturation mutagenesis of the WSXWS motif of the erythropoietin receptor, JOURNAL OF BIOLOGICAL CHEMISTRY 271, 4699 (1996). (10.1074/jbc.271.9.4699) / JOURNAL OF BIOLOGICAL CHEMISTRY / Saturation mutagenesis of the WSXWS motif of the erythropoietin receptor by HILTON D.J. (1996)
  27. HILTON D.J., INCREASED CELL-SURFACE EXPRESSION AND ENHANCED FOLDING IN THE ENDOPLASMIC-RETICULUM OF A MUTANT ERYTHROPOIETIN RECEPTOR, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 92, 190 (1995). (10.1073/pnas.92.1.190) / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA / INCREASED CELL-SURFACE EXPRESSION AND ENHANCED FOLDING IN THE ENDOPLASMIC-RETICULUM OF A MUTANT ERYTHROPOIETIN RECEPTOR by HILTON D.J. (1995)
  28. HOLMGREN A, CRYSTAL-STRUCTURE OF CHAPERONE PROTEIN PAPD REVEALS AN IMMUNOGLOBULIN FOLD, NATURE 342, 248 (1989). (10.1038/342248a0) / NATURE / CRYSTAL-STRUCTURE OF CHAPERONE PROTEIN PAPD REVEALS AN IMMUNOGLOBULIN FOLD by HOLMGREN A (1989)
  29. HOWARD A.J., THE USE OF AN IMAGING PROPORTIONAL COUNTER IN MACROMOLECULAR CRYSTALLOGRAPHY, JOURNAL OF APPLIED CRYSTALLOGRAPHY 20, 383 (1987). (10.1107/S0021889887086436) / JOURNAL OF APPLIED CRYSTALLOGRAPHY / THE USE OF AN IMAGING PROPORTIONAL COUNTER IN MACROMOLECULAR CRYSTALLOGRAPHY by HOWARD A.J. (1987)
  30. HUBER A.H., CRYSTAL-STRUCTURE OF TANDEM TYPE-III FIBRONECTIN DOMAINS FROM DROSOPHILA NEUROGLIAN AT 2.0 ANGSTROM, NEURON 12, 717 (1994). (10.1016/0896-6273(94)90326-3) / NEURON / CRYSTAL-STRUCTURE OF TANDEM TYPE-III FIBRONECTIN DOMAINS FROM DROSOPHILA NEUROGLIAN AT 2.0 ANGSTROM by HUBER A.H. (1994)
  31. IHLE J.N., SEMIN IMMUNOL 5, 375 (1993). (10.1006/smim.1993.1043) / SEMIN IMMUNOL by IHLE J.N. (1993)
  32. JACOBS K, ISOLATION AND CHARACTERIZATION OF GENOMIC AND CDNA CLONES OF HUMAN ERYTHROPOIETIN, NATURE 313, 806 (1985). (10.1038/313806a0) / NATURE / ISOLATION AND CHARACTERIZATION OF GENOMIC AND CDNA CLONES OF HUMAN ERYTHROPOIETIN by JACOBS K (1985)
  33. JACOBSON L.O., ROLE OF THE KIDNEY IN ERYTHROPOIESIS, NATURE 179, 633 (1957). (10.1038/179633a0) / NATURE / ROLE OF THE KIDNEY IN ERYTHROPOIESIS by JACOBSON L.O. (1957)
  34. JOHNSON D.L., Refolding, purification, and characterization of human erythropoietin binding protein produced in Escherichia coli, PROTEIN EXPRESSION AND PURIFICATION 7, 104 (1996). (10.1006/prep.1996.0014) / PROTEIN EXPRESSION AND PURIFICATION / Refolding, purification, and characterization of human erythropoietin binding protein produced in Escherichia coli by JOHNSON D.L. (1996)
  35. JOHNSON D.L. unpublished data.
  36. JOLLIFFE L.K., ERYTHROPOIETIN RECEPTOR - APPLICATION IN DRUG DEVELOPMENT, NEPHROLOGY DIALYSIS TRANSPLANTATION 10, 28 (1995). (10.1093/ndt/10.supp2.28) / NEPHROLOGY DIALYSIS TRANSPLANTATION / ERYTHROPOIETIN RECEPTOR - APPLICATION IN DRUG DEVELOPMENT by JOLLIFFE L.K. (1995)
  37. JONES T.A., IMPROVED METHODS FOR BUILDING PROTEIN MODELS IN ELECTRON-DENSITY MAPS AND THE LOCATION OF ERRORS IN THESE MODELS, ACTA CRYSTALLOGRAPHICA SECTION A 47, 110 (1991). (10.1107/S0108767390010224) / ACTA CRYSTALLOGRAPHICA SECTION A / IMPROVED METHODS FOR BUILDING PROTEIN MODELS IN ELECTRON-DENSITY MAPS AND THE LOCATION OF ERRORS IN THESE MODELS by JONES T.A. (1991)
  38. KIM H, X-RAY CRYSTALLOGRAPHIC DETERMINATION OF THE STRUCTURE OF BOVINE LENS LEUCINE AMINOPEPTIDASE COMPLEXED WITH AMASTATIN - FORMULATION OF A CATALYTIC MECHANISM FEATURING A GEM-DIOLATE TRANSITION-STATE, BIOCHEMISTRY 32, 8465 (1993). (10.1021/bi00084a011) / BIOCHEMISTRY / X-RAY CRYSTALLOGRAPHIC DETERMINATION OF THE STRUCTURE OF BOVINE LENS LEUCINE AMINOPEPTIDASE COMPLEXED WITH AMASTATIN - FORMULATION OF A CATALYTIC MECHANISM FEATURING A GEM-DIOLATE TRANSITION-STATE by KIM H (1993)
  39. KLINGMULLER U, SPECIFIC RECRUITMENT OF SH-PTP1 TO THE ERYTHROPOIETIN RECEPTOR CAUSES INACTIVATION OF JAK2 AND TERMINATION OF PROLIFERATIVE SIGNALS, CELL 80, 729 (1995). (10.1016/0092-8674(95)90351-8) / CELL / SPECIFIC RECRUITMENT OF SH-PTP1 TO THE ERYTHROPOIETIN RECEPTOR CAUSES INACTIVATION OF JAK2 AND TERMINATION OF PROLIFERATIVE SIGNALS by KLINGMULLER U (1995)
  40. 10.1182/blood.V77.3.419.419
  41. 10.1107/S0021889891004399
  42. 10.1126/science.8378771
  43. 10.1126/science.1279805
  44. LEE B, INTERPRETATION OF PROTEIN STRUCTURES - ESTIMATION OF STATIC ACCESSIBILITY, JOURNAL OF MOLECULAR BIOLOGY 55, 379 (1971). (10.1016/0022-2836(71)90324-X) / JOURNAL OF MOLECULAR BIOLOGY / INTERPRETATION OF PROTEIN STRUCTURES - ESTIMATION OF STATIC ACCESSIBILITY by LEE B (1971)
  45. MATTHEWS B.W., SOLVENT CONTENT OF PROTEIN CRYSTALS, JOURNAL OF MOLECULAR BIOLOGY 33, 491 (1968). (10.1016/0022-2836(68)90205-2) / JOURNAL OF MOLECULAR BIOLOGY / SOLVENT CONTENT OF PROTEIN CRYSTALS by MATTHEWS B.W. (1968)
  46. MCDONALD I.K., SATISFYING HYDROGEN-BONDING POTENTIAL IN PROTEINS, JOURNAL OF MOLECULAR BIOLOGY 238, 777 (1994). (10.1006/jmbi.1994.1334) / JOURNAL OF MOLECULAR BIOLOGY / SATISFYING HYDROGEN-BONDING POTENTIAL IN PROTEINS by MCDONALD I.K. (1994)
  47. MIDDLETON S.A., Identification of a critical ligand binding determinant of the human erythropoietin receptor - Evidence for common ligand binding motifs in the cytokine receptor family, JOURNAL OF BIOLOGICAL CHEMISTRY 271, 14045 (1996). (10.1074/jbc.271.24.14045) / JOURNAL OF BIOLOGICAL CHEMISTRY / Identification of a critical ligand binding determinant of the human erythropoietin receptor - Evidence for common ligand binding motifs in the cytokine receptor family by MIDDLETON S.A. (1996)
  48. MIYAZAKI T, THE INTEGRITY OF THE CONSERVED WS MOTIF COMMON TO IL-2 AND OTHER CYTOKINE RECEPTORS IS ESSENTIAL FOR LIGAND-BINDING AND SIGNAL TRANSDUCTION, EMBO JOURNAL 10, 3191 (1991). (10.1002/j.1460-2075.1991.tb04881.x) / EMBO JOURNAL / THE INTEGRITY OF THE CONSERVED WS MOTIF COMMON TO IL-2 AND OTHER CYTOKINE RECEPTORS IS ESSENTIAL FOR LIGAND-BINDING AND SIGNAL TRANSDUCTION by MIYAZAKI T (1991)
  49. MULLER Y.A., STRUCTURE OF THE EXTRACELLULAR DOMAIN OF HUMAN TISSUE FACTOR - LOCATION OF THE FACTOR VIIA BINDING-SITE, BIOCHEMISTRY 33, 10864 (1994). (10.1021/bi00202a003) / BIOCHEMISTRY / STRUCTURE OF THE EXTRACELLULAR DOMAIN OF HUMAN TISSUE FACTOR - LOCATION OF THE FACTOR VIIA BINDING-SITE by MULLER Y.A. (1994)
  50. NICHOLLS A, PROTEIN FOLDING AND ASSOCIATION - INSIGHTS FROM THE INTERFACIAL AND THERMODYNAMIC PROPERTIES OF HYDROCARBONS, PROTEINS-STRUCTURE FUNCTION AND GENETICS 11, 281 (1991). (10.1002/prot.340110407) / PROTEINS-STRUCTURE FUNCTION AND GENETICS / PROTEIN FOLDING AND ASSOCIATION - INSIGHTS FROM THE INTERFACIAL AND THERMODYNAMIC PROPERTIES OF HYDROCARBONS by NICHOLLS A (1991)
  51. OTWINOWSKI Z, DATA COLLECTION PROC: 56 (1993). / DATA COLLECTION PROC by OTWINOWSKI Z (1993)
  52. PHILO J.S., Dimerization of the extracellular domain of the erythropoietin (EPO) receptor by EPO: One high-affinity and one low-affinity interaction, BIOCHEMISTRY 35, 1681 (1996). (10.1021/bi9524272) / BIOCHEMISTRY / Dimerization of the extracellular domain of the erythropoietin (EPO) receptor by EPO: One high-affinity and one low-affinity interaction by PHILO J.S. (1996)
  53. QUELLE D.E., MUTATIONS IN THE WSAWSE AND CYTOSOLIC DOMAINS OF THE ERYTHROPOIETIN RECEPTOR AFFECT SIGNAL TRANSDUCTION AND LIGAND-BINDING AND INTERNALIZATION, MOLECULAR AND CELLULAR BIOLOGY 12, 4553 (1992). / MOLECULAR AND CELLULAR BIOLOGY / MUTATIONS IN THE WSAWSE AND CYTOSOLIC DOMAINS OF THE ERYTHROPOIETIN RECEPTOR AFFECT SIGNAL TRANSDUCTION AND LIGAND-BINDING AND INTERNALIZATION by QUELLE D.E. (1992)
  54. READ R.J., IMPROVED FOURIER COEFFICIENTS FOR MAPS USING PHASES FROM PARTIAL STRUCTURES WITH ERRORS, ACTA CRYSTALLOGRAPHICA SECTION A 42, 140 (1986). (10.1107/S0108767386099622) / ACTA CRYSTALLOGRAPHICA SECTION A / IMPROVED FOURIER COEFFICIENTS FOR MAPS USING PHASES FROM PARTIAL STRUCTURES WITH ERRORS by READ R.J. (1986)
  55. RICHARDSON J.S., ADV PROTEIN CHEM 34, 167 (1981). (10.1016/S0065-3233(08)60520-3) / ADV PROTEIN CHEM by RICHARDSON J.S. (1981)
  56. RONCO L.V., IDENTIFICATION OF CONSERVED AMINO-ACIDS IN THE HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR-ALPHA SUBUNIT CRITICAL FOR FUNCTION - EVIDENCE FOR FORMATION OF A HETERODIMERIC RECEPTOR COMPLEX PRIOR TO LIGAND-BINDING, JOURNAL OF BIOLOGICAL CHEMISTRY 269, 277 (1994). (10.1016/S0021-9258(17)42346-5) / JOURNAL OF BIOLOGICAL CHEMISTRY / IDENTIFICATION OF CONSERVED AMINO-ACIDS IN THE HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR-ALPHA SUBUNIT CRITICAL FOR FUNCTION - EVIDENCE FOR FORMATION OF A HETERODIMERIC RECEPTOR COMPLEX PRIOR TO LIGAND-BINDING by RONCO L.V. (1994)
  57. RYU S.E., CRYSTAL-STRUCTURE OF AN HIV-BINDING RECOMBINANT FRAGMENT OF HUMAN CD4, NATURE 348, 419 (1990). (10.1038/348419a0) / NATURE / CRYSTAL-STRUCTURE OF AN HIV-BINDING RECOMBINANT FRAGMENT OF HUMAN CD4 by RYU S.E. (1990)
  58. SOMERS W, THE X-RAY STRUCTURE OF A GROWTH-HORMONE PROLACTIN RECEPTOR COMPLEX, NATURE 372, 478 (1994). (10.1038/372478a0) / NATURE / THE X-RAY STRUCTURE OF A GROWTH-HORMONE PROLACTIN RECEPTOR COMPLEX by SOMERS W (1994)
  59. SPIVAK J.L., ERYTHROPOIETIN BASIC 8, 863 (1994). / ERYTHROPOIETIN BASIC by SPIVAK J.L. (1994)
  60. STURA E.A. unpublished data.
  61. WALTER M.R., CRYSTAL-STRUCTURE OF A COMPLEX BETWEEN INTERFERON-GAMMA AND ITS SOLUBLE HIGH-AFFINITY RECEPTOR, NATURE 376, 230 (1995). (10.1038/376230a0) / NATURE / CRYSTAL-STRUCTURE OF A COMPLEX BETWEEN INTERFERON-GAMMA AND ITS SOLUBLE HIGH-AFFINITY RECEPTOR by WALTER M.R. (1995)
  62. WANG J.H., ATOMIC-STRUCTURE OF A FRAGMENT OF HUMAN CD4 CONTAINING 2 IMMUNOGLOBULIN-LIKE DOMAINS, NATURE 348, 411 (1990). (10.1038/348411a0) / NATURE / ATOMIC-STRUCTURE OF A FRAGMENT OF HUMAN CD4 CONTAINING 2 IMMUNOGLOBULIN-LIKE DOMAINS by WANG J.H. (1990)
  63. WATOWICH S.S., ACTIVATION AND INHIBITION OF ERYTHROPOIETIN RECEPTOR FUNCTION - ROLE OF RECEPTOR DIMERIZATION, MOLECULAR AND CELLULAR BIOLOGY 14, 3535 (1994). / MOLECULAR AND CELLULAR BIOLOGY / ACTIVATION AND INHIBITION OF ERYTHROPOIETIN RECEPTOR FUNCTION - ROLE OF RECEPTOR DIMERIZATION by WATOWICH S.S. (1994)
  64. WATOWICH S.S., HOMODIMERIZATION AND CONSTITUTIVE ACTIVATION OF THE ERYTHROPOIETIN RECEPTOR, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89, 2140 (1992). (10.1073/pnas.89.6.2140) / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA / HOMODIMERIZATION AND CONSTITUTIVE ACTIVATION OF THE ERYTHROPOIETIN RECEPTOR by WATOWICH S.S. (1992)
  65. WELLS J.A., STRUCTURAL AND FUNCTIONAL BASIS FOR HORMONE-BINDING AND RECEPTOR OLIGOMERIZATION, CURRENT OPINION IN CELL BIOLOGY 6, 163 (1994). (10.1016/0955-0674(94)90132-5) / CURRENT OPINION IN CELL BIOLOGY / STRUCTURAL AND FUNCTIONAL BASIS FOR HORMONE-BINDING AND RECEPTOR OLIGOMERIZATION by WELLS J.A. (1994)
  66. WELLS J.A., Binding in the growth hormone receptor complex, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 93, 1 (1996). (10.1073/pnas.93.1.1) / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA / Binding in the growth hormone receptor complex by WELLS J.A. (1996)
  67. WILSON I.A., STRUCTURAL ASPECTS OF ANTIBODIES AND ANTIBODY-ANTIGEN COMPLEXES, CIBA FOUNDATION SYMPOSIA 159, 13 (1991). / CIBA FOUNDATION SYMPOSIA / STRUCTURAL ASPECTS OF ANTIBODIES AND ANTIBODY-ANTIGEN COMPLEXES by WILSON I.A. (1991)
  68. 10.1126/science.273.5274.458
  69. YOSHIMURA A, MUTATIONS IN THE TRP-SER-X-TRP-SER MOTIF OF THE ERYTHROPOIETIN RECEPTOR ABOLISH PROCESSING, LIGAND-BINDING, AND ACTIVATION OF THE RECEPTOR, JOURNAL OF BIOLOGICAL CHEMISTRY 267, 11619 (1992). (10.1016/S0021-9258(19)49956-0) / JOURNAL OF BIOLOGICAL CHEMISTRY / MUTATIONS IN THE TRP-SER-X-TRP-SER MOTIF OF THE ERYTHROPOIETIN RECEPTOR ABOLISH PROCESSING, LIGAND-BINDING, AND ACTIVATION OF THE RECEPTOR by YOSHIMURA A (1992)
Dates
Type When
Created 18 years, 10 months ago (Oct. 27, 2006, 2:30 p.m.)
Deposited 1 year, 7 months ago (Jan. 12, 2024, 11:21 p.m.)
Indexed 4 weeks ago (Aug. 2, 2025, 12:24 a.m.)
Issued 29 years, 1 month ago (July 26, 1996)
Published 29 years, 1 month ago (July 26, 1996)
Published Print 29 years, 1 month ago (July 26, 1996)
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@article{Livnah_1996, title={Functional Mimicry of a Protein Hormone by a Peptide Agonist: The EPO Receptor Complex at 2.8 Å}, volume={273}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.273.5274.464}, DOI={10.1126/science.273.5274.464}, number={5274}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Livnah, Oded and Stura, Enrico A. and Johnson, Dana L. and Middleton, Steven A. and Mulcahy, Linda S. and Wrighton, Nicholas C. and Dower, William J. and Jolliffe, Linda K. and Wilson, Ian A.}, year={1996}, month=jul, pages={464–471} }