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