Crystal Structure of the Ephrin-B1 Ectodomain: Implications for Receptor Recognition and Signaling

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• 作者：Dimitar B. Nikolov ; Chen Li ; William A. Barton ; and Juha-Pekka Himanen
• 刊名：Biochemistry
• 出版年：2005
• 出版时间：August 23, 2005
• 年：2005
• 卷：44
• 期：33
• 页码：10947 - 10953
• 全文大小：367K
• 年卷期：v.44,no.33(August 23, 2005)
• ISSN：1520-4995

文摘

Eph receptors and their ephrin ligands are involved in various aspects of cell-cellcommunication during development, including axonal pathfinding in the nervous system and cell-cellinteractions of the vascular endothelial cells. Recent structural studies revealed unique molecular features,not previously seen in any other receptor-ligand families, and explained many of the biochemical andsignaling properties of Ephs and ephrins. However, unresolved questions remain regarding the potentialoligomerization and clustering of these important signaling molecules. In this study, the biophysicalproperties and receptor-binding preferences of the extracellular domain of ephrin-B1 were investigatedand its crystal structure was determined at 2.65 Å resolution. Ephrin-B1 is a monomer both in solutionand in the crystals, while it was previously shown that the closely related ephrin-B2 forms homodimers.The main structural difference between ephrin-B1 and ephrin-B2 is the conformation of the receptor-binding G-H loop and the partially disordered N-terminal tetramerization region of ephrin-B1. The G-Hloop is structurally rigid in ephrin-B2 and adopts the same conformation in both the receptor-bound andunbound ligand, where it mediates receptor-independent homodimerization. In the ephrin-B1 structure,on the other hand, the G-H loop is not involved in any homotypic interactions and adopts a new, distinctconformation. The implications of the ephrin-B1 structure, in context of available ephrin-B1 mutagenesisdata, for the mechanism of Eph-ephrin recognition and signaling initiation are discussed.