Ephrin growth factors are attached to the membrane by either GPI-anchor or transmembrane domains and are known to signal bi-directionally: cells, expressing the ephrins experience the downstream signaling in response to ephrin recognition by their receptor, Eph. This bidirectionality makes ephrins an interesting drug target. In the present work, we investigate the role played by conformational heterogeneity and juxtamembrane domains of Ephrin A1 in its interactions with the ligand-binding domain of EphA2 receptor by NMR spectroscopy. We show that ligand recognition occurs via a conformational selection mechanism and that the juxtamembrane regions are flexible, unstructured and are not involved in the binding
