Crystallographic Evidence for Preformed Dimers of Erythropoietin Receptor Before Ligand Activation

• DOI: 10.1126/science.283.5404.987
• Publication Date: 2002-07-27T09:40:50Z
• Authors: Oded Livnah; Enrico A. Stura; Steven A. Middleton; Dana L. Johnson; Linda K. Jolliffe; Ian A. Wilson
• Keywords: Erythropoietin receptor

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