Crystal structure of an Eph receptor-ephrin complex

Nature. 2001 Dec 20-27;414(6866):933-8. doi: 10.1038/414933a.

Abstract

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 epithelia. Here we report the crystal structure of the complex formed between EphB2 and ephrin-B2, determined at 2.7 A 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Dimerization
  • Ephrin-B2
  • Escherichia coli
  • Ligands
  • Macromolecular Substances
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Receptor Protein-Tyrosine Kinases / chemistry*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, EphB2
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment

Substances

  • Ephrin-B2
  • Ligands
  • Macromolecular Substances
  • Membrane Proteins
  • Recombinant Proteins
  • Receptor Protein-Tyrosine Kinases
  • Receptor, EphB2