Computational analysis of ligand–receptor interactions in wild-type and mutant erythropoietin complexes

Erythropoietin (EPO), a pleiotropic cytokine, binds to its receptor (EPOR) in bone marrow, activating a signaling cascade that results in red blood cell proliferation. A recently discovered naturally occurring EPO mutation (R150Q) at active site 1 (AS1) of the protein was shown to attenuate its canonical downstream signaling, eliminating its hematopoietic effects and causing a fatal anemia. The purpose of this work was to analyze the EPO–EPOR complex computationally to provide a structural explanation for this signaling change