Structural Plasticity of Eph Receptor A4 Facilitates Cross-Class Ephrin Signaling
Structural Plasticity of Eph Receptor A4 Facilitates Cross-Class Ephrin Signaling
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DOI：
10.1016/j.str.2009.07.018
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发表时间：
2009-10-14
期刊：
影响因子：
5.7
通讯作者：
Jones, E. Yvonne
中科院分区：
文献类型：
--
作者：
Bowden, Thomas A.;Aricescu, A. Radu;Jones, E. Yvonne
EphA4酪氨酸激酶细胞表面受体调节一系列生理过程，并且是目前已知的唯一以高亲和力结合A和B类肝配蛋白的A类Eph受体。我们已经解决了EphA4配体结合结构域单独和与（1）ephrinB2和（2）ephrinA2复合的晶体结构。这组结构显示EphA4在其配体结合面中具有显著的构象可塑性。体外结合数据表明，它对A类配体的亲和力高于B类配体。利用先前报道的Eph受体结构进行的结构分析表明，EphA4在分离时和与ephrinA2复合时类似于其他A类Eph受体，但在结合ephrinB2时呈现B类Eph受体的结构特征。这种相互作用的可塑性揭示了EphA4作为结构变色龙，能够采用A和B类Eph受体构象，从而为EphA型跨类反应性提供了分子基础。
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.