3ETP

The crystal structure of the ligand-binding domain of the EphB2 receptor at 2.0 A resolution

3ETP の概要

• エントリーDOI: 10.2210/pdb3etp/pdb
• 関連するPDBエントリー: 1KGY 1NUK 1SHW 2QBX
• 分子名称: Ephrin type-B receptor 2 (2 entities in total)
• 機能のキーワード: eph receptor, tyrosine kinase, alternative splicing, atp-binding, glycoprotein, kinase, membrane, nucleotide-binding, phosphoprotein, receptor, transferase, transmembrane, tyrosine-protein kinase
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P54763
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21437.21

構造登録者

Goldgur, Y.,Paavilainen, S.,Nikolov, D.B.,Himanen, J.P. (登録日: 2008-10-08, 公開日: 2008-10-21, 最終更新日: 2024-11-06)

主引用文献

Goldgur, Y.,Paavilainen, S.,Nikolov, D.,Himanen, J.P.
Structure of the ligand-binding domain of the EphB2 receptor at 2 A resolution.
Acta Crystallogr.,Sect.F, 65:71-74, 2009

PubMed Abstract: Eph tyrosine kinase receptors, the largest group of receptor tyrosine kinases, and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape and mobility. Recently, several Eph receptors and ephrins have also been found to play important roles in the progression of cancer. Structural and biophysical studies have established detailed information on the binding and recognition of Eph receptors and ephrins. The initial high-affinity binding of Eph receptors to ephrin occurs through the penetration of an extended G-H loop of the ligand into a hydrophobic channel on the surface of the receptor. Consequently, the G-H loop-binding channel of Eph receptors is the main target in the search for Eph antagonists that could be used in the development of anticancer drugs and several peptides have been shown to specifically bind Eph receptors and compete with the cognate ephrin ligands. However, the molecular details of the conformational changes upon Eph/ephrin binding have remained speculative, since two of the loops were unstructured in the original model of the free EphB2 structure and their conformational changes upon ligand binding could consequently not be analyzed in detail. In this study, the X-ray structure of unbound EphB2 is reported at a considerably higher 2 A resolution, the conformational changes that the important receptor loops undergo upon ligand binding are described and the consequences that these findings have for the development of Eph antagonists are discussed.

PubMed: 19193989
DOI: 10.1107/S1744309108043078

実験手法

X-RAY DIFFRACTION (2 Å)