Crystal structure of an Eph receptor–ephrin complex

The Eph family of receptor tyrosine kinases and their membrane-anchored ephrin ligands are important in regulating cell–cell interactions as they initiate a unique bidirectional signal transduction cascade whereby information is communicated into both the Eph-expressing and the ephrin-expressing cells. Initially identified as regulators of axon pathfinding and neuronal cell migration, Ephs and ephrins are now known to have roles in many other cell–cell interactions, including those of vascular endothelial cells and specialized epithelia1,2. Here we report the crystal structure of the complex formed between EphB2 and ephrin-B2, determined at 2.7 Å resolution. Each Eph receptor binds an ephrin ligand through an expansive dimerization interface dominated by the insertion of an extended ephrin loop into a channel at the surface of the receptor. Two Eph–Ephrin dimers then join to form a tetramer, in which each ligand interacts with two receptors and each receptor interacts with two ligands. The Eph and ephrin molecules are precisely positioned and orientated in these complexes, promoting higher-order clustering and the initiation of bidirectional signalling.