Structural plasticity of eph receptor A4 facilitates cross-class ephrin signaling

Thomas A Bowden, Alexandru R Aricescu, Joanne E Nettleship, Christian Siebold, Nahir Rahman-Huq, Raymond J Owens, David I Stuart, E Yvonne Jones

Research output: Contribution to journalArticlepeer-review


The EphA4 tyrosine kinase cell surface receptor regulates an array of physiological processes and is the only currently known class A Eph receptor that binds both A and B class ephrins with high affinity. We have solved the crystal structure of the EphA4 ligand binding domain alone and in complex with (1) ephrinB2 and (2) ephrinA2. This set of structures shows that EphA4 has significant conformational plasticity in its ligand binding face. In vitro binding data demonstrate that it has a higher affinity for class A than class B ligands. Structural analyses, drawing on previously reported Eph receptor structures, show that EphA4 in isolation and in complex with ephrinA2 resembles other class A Eph receptors but on binding ephrinB2 assumes structural hallmarks of the class B Eph receptors. This interactive plasticity reveals EphA4 as a structural chameleon, able to adopt both A and B class Eph receptor conformations, and thus provides a molecular basis for EphA-type cross-class reactivity.
Original languageEnglish
Pages (from-to)1386-97
Number of pages10
Issue number10
Publication statusPublished - Oct 2009


  • Amino Acid Sequence
  • Binding Sites
  • Ephrins
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Receptor, EphA4
  • Signal Transduction
  • Structure-Activity Relationship

Fingerprint Dive into the research topics of 'Structural plasticity of eph receptor A4 facilitates cross-class ephrin signaling'. Together they form a unique fingerprint.

Cite this