Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

552 Scopus citations


Erythropoietin receptor (EPOR) is thought to be activated by ligand- induced homodimerization. However, structures of agonist 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.

Original languageAmerican English
Pages (from-to)987-990
Number of pages4
Issue number5404
StatePublished - 12 Feb 1999


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