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Science 12 February 1999:
Vol. 283. no. 5404, pp. 987 - 990
DOI: 10.1126/science.283.5404.987
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Reports

Crystallographic Evidence for Preformed Dimers of Erythropoietin Receptor Before Ligand Activation

Oded Livnah, 1* Enrico A. Stura, 1dagger Steven A. Middleton, 2 Dana L. Johnson, 2 Linda K. Jolliffe, 2ddagger Ian A. Wilson 1ddagger

Erythropoietin receptor (EPOR) is thought to be activated by ligand-induced homodimerization. However, structures of agonist and antagonist peptide complexes of EPOR, as well as an EPO-EPOR complex, have shown that the actual dimer configuration is critical for the biological response and signal efficiency. The crystal structure of the extracellular domain of EPOR in its unliganded form at 2.4 angstrom resolution has revealed a dimer in which the individual membrane-spanning and intracellular domains would be too far apart to permit phosphorylation by JAK2. This unliganded EPOR dimer is formed from self-association of the same key binding site residues that interact with EPO-mimetic peptide and EPO ligands. This model for a preformed dimer on the cell surface provides insights into the organization, activation, and plasticity of recognition of hematopoietic cell surface receptors.

1 Department of Molecular Biology and Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road., La Jolla, CA 92037, USA.
2 R. W. Johnson Pharmaceutical Research Institute, Drug Discovery Research, 1000 Route 202, Box 300, Raritan, NJ 08869, USA.
*   Present address: Department of Biological Chemistry, Institute of Life Sciences, Wolfson Centre for applied Structural Biology, Hebrew University of Jerusalem, Jerusalem 91904, Israel.

dagger    Present address: Department d'Ingenierie et d'Etude des Proteines, BAT 152 C.E.A./SACLAY, 91191 Gif sur Yvette Cedex, France.

ddagger    To whom correspondence should be addressed.

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   Abstract »    Full Text »    PDF »
Binding and Functional Studies with the Growth Hormone Receptor Antagonist, B2036-PEG (Pegvisomant), Reveal Effects of Pegylation and Evidence That It Binds to a Receptor Dimer.
R. J. M. Ross, K. C. Leung, M. Maamra, W. Bennett, N. Doyle, M. J. Waters, and K. K. Y. Ho (2001)
J. Clin. Endocrinol. Metab. 86, 1716-1723
   Abstract »    Full Text »
Regulation of Escherichia coli RelA Requires Oligomerization of the C-Terminal Domain.
M. Gropp, Y. Strausz, M. Gross, and G. Glaser (2001)
J. Bacteriol. 183, 570-579
   Abstract »    Full Text »    PDF »
Two Different Epitopes of the Signal Transducer gp130 Sequentially Cooperate on IL-6-Induced Receptor Activation.
S. Pflanz, I. Kurth, J. Grotzinger, P. C. Heinrich, and G. Muller-Newen (2000)
J. Immunol. 165, 7042-7049
   Abstract »    Full Text »    PDF »
Friend erythroleukemia revisited.
P. A. Ney and A. D. D'Andrea (2000)
Blood 96, 3675-3680
   Full Text »    PDF »
Rotational Coupling of the Transmembrane and Kinase Domains of the Neu Receptor Tyrosine Kinase.
C. A. Bell, J. A. Tynan, K. C. Hart, A. N. Meyer, S. C. Robertson, and D. J. Donoghue (2000)
Mol. Biol. Cell 11, 3589-3599
   Abstract »    Full Text »
Erythropoietin mimetic peptides and the future.
D. L. Johnson and L. K. Jolliffe (2000)
Nephrol. Dial. Transplant. 15, 1274-1277
   Full Text »    PDF »
A Domain in TNF Receptors That Mediates Ligand-Independent Receptor Assembly and Signaling.
F. K.-M. Chan, H. J. Chun, L. Zheng, R. M. Siegel, K. L. Bui, and M. J. Lenardo (2000)
Science 288, 2351-2354
   Abstract »    Full Text »
Growth Hormone (GH)-independent Dimerization of GH Receptor by a Leucine Zipper Results in Constitutive Activation.
S. N. Behncken, N. Billestrup, R. Brown, J. Amstrup, B. Conway-Campbell, and M. J. Waters (2000)
J. Biol. Chem. 275, 17000-17007
   Abstract »    Full Text »    PDF »
Activation of Downstream Signals by the Long Form of the Leptin Receptor.
A. S. Banks, S. M. Davis, S. H. Bates, and M. G. Myers Jr. (2000)
J. Biol. Chem. 275, 14563-14572
   Abstract »    Full Text »    PDF »
Genuine Monovalent Ligands of TrkA Nerve Growth Factor Receptors Reveal a Novel Pharmacological Mechanism of Action.
S. Maliartchouk, T. Debeir, N. Beglova, A. C. Cuello, K. Gehring, and H. U. Saragovi (2000)
J. Biol. Chem. 275, 9946-9956
   Abstract »    Full Text »    PDF »
Bone Morphogenetic Protein Receptor Complexes on the Surface of Live Cells: A New Oligomerization Mode for Serine/Threonine Kinase Receptors.
L. Gilboa, A. Nohe, T. Geissendörfer, W. Sebald, Y. I. Henis, and P. Knaus (2000)
Mol. Biol. Cell 11, 1023-1035
   Abstract »    Full Text »
Studies on the Interleukin-6-type Cytokine Signal Transducer gp130 Reveal a Novel Mechanism of Receptor Activation by Monoclonal Antibodies.
G. Muller-Newen, A. Kuster, J. Wijdenes, F. Schaper, and P. C. Heinrich (2000)
J. Biol. Chem. 275, 4579-4586
   Abstract »    Full Text »    PDF »
The SH2 Inositol 5-Phosphatase Ship1 Is Recruited in an SH2-dependent Manner to the Erythropoietin Receptor.
J. M. Mason, B. K. Beattie, Q. Liu, D. J. Dumont, and D. L. Barber (2000)
J. Biol. Chem. 275, 4398-4406
   Abstract »    Full Text »    PDF »
A Designed Peptidomimetic Agonistic Ligand of TrkA Nerve Growth Factor Receptors.
S. Maliartchouk, Y. Feng, L. Ivanisevic, T. Debeir, A. C. Cuello, K. Burgess, and H. U. Saragovi (2000)
Mol. Pharmacol. 57, 385-391
   Abstract »    Full Text »
Kinetics of T-cell Receptor Binding by Bivalent HLA-DR{middle dot}Peptide Complexes That Activate Antigen-specific Human T-cells.
H. Appel, L. Gauthier, J. Pyrdol, and K. W. Wucherpfennig (2000)
J. Biol. Chem. 275, 312-321
   Abstract »    Full Text »    PDF »
Dimerization of the Interferon Type I Receptor IFNaR2-2 Is Sufficient for Induction of Interferon Effector Genes but Not for Full Antiviral Activity.
E. Pattyn, X. Van Ostade, L. Schauvliege, A. Verhee, M. Kalai, J. Vandekerckhove, and J. Tavernier (1999)
J. Biol. Chem. 274, 34838-34845
   Abstract »    Full Text »    PDF »
Functional Analysis of a Single Chain Chimeric alpha /beta -Granulocyte-Macrophage Colony-stimulating Factor Receptor. IMPORTANCE OF A GLUTAMATE RESIDUE IN THE TRANSMEMBRANE REGION.
S. Kafert, S. Luther, I. Boll, K. Wagner, A. Ganser, and M. Eder (1999)
J. Biol. Chem. 274, 33064-33071
   Abstract »    Full Text »    PDF »


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