Crystal structure of an Eph receptor-ephrin complex
Crystal structure of an Eph receptor-ephrin complex
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DOI：
10.1038/414933a
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发表时间：
2001-12-20
期刊：
影响因子：
64.8
通讯作者：
Nikolov, DB
中科院分区：
文献类型：
--
作者：
Himanen, JP;Rajashankar, KR;Nikolov, DB
受体酪氨酸激酶的Eph家族和它们的膜锚定肝配蛋白配体在调节细胞-细胞相互作用中是重要的，因为它们启动独特的双向信号转导级联，由此信息被传递到表达Eph和表达肝配蛋白的细胞中。Ephs和ephrin最初被鉴定为轴突寻路和神经元细胞迁移的调节剂，现在已知它们在许多其他细胞-细胞相互作用中发挥作用，包括血管内皮细胞和特化上皮细胞的相互作用（1，2）。在这里，我们报告的晶体结构的EphB 2和ephrin-B2之间形成的复合物，确定在2.7埃分辨率。每个Eph受体通过扩展的二聚化界面结合肝配蛋白配体，所述界面由延伸的肝配蛋白环插入受体表面的通道主导。然后两个Eph-Ephrin二聚体结合形成四聚体，其中每个配体与两个受体相互作用，每个受体与两个配体相互作用。Eph和ephrin分子在这些复合物中精确定位和定向，促进高阶聚类和双向信号传导的启动。
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(1,2). Here we report the crystal structure of the complex formed between EphB2 and ephrin-B2, determined at 2.7 Angstrom 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.