3HPN

Ligand recognition by A-class EPH receptors: crystal structures of the EPHA2 ligand-binding domain and the EPHA2/EPHRIN-A1 complex

3HPN の概要

• エントリーDOI: 10.2210/pdb3hpn/pdb
• 分子名称: Ephrin type-A receptor 2 (2 entities in total)
• 機能のキーワード: eph receptor tyrosine kinase, ephrin, atp-binding, glycoprotein, kinase, membrane, nucleotide-binding, phosphoprotein, receptor, transferase, transmembrane, tyrosine-protein kinase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P29317
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 119481.55

構造登録者

Himanen, J.P.,Goldgur, Y.,Miao, H.,Myshkin, E.,Guo, H.,Buck, M.,Nguyen, M.,Rajashankar, K.R.,Wang, B.,Nikolov, D.B. (登録日: 2009-06-04, 公開日: 2009-06-30, 最終更新日: 2024-11-20)

主引用文献

Himanen, J.P.,Goldgur, Y.,Miao, H.,Myshkin, E.,Guo, H.,Buck, M.,Nguyen, M.,Rajashankar, K.R.,Wang, B.,Nikolov, D.B.
Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex.
Embo Rep., 10:722-728, 2009

PubMed Abstract: Ephrin (Eph) receptor tyrosine kinases fall into two subclasses (A and B) according to preferences for their ephrin ligands. All published structural studies of Eph receptor/ephrin complexes involve B-class receptors. Here, we present the crystal structures of an A-class complex between EphA2 and ephrin-A1 and of unbound EphA2. Although these structures are similar overall to their B-class counterparts, they reveal important differences that define subclass specificity. The structures suggest that the A-class Eph receptor/ephrin interactions involve smaller rearrangements in the interacting partners, better described by a 'lock-and-key'-type binding mechanism, in contrast to the 'induced fit' mechanism defining the B-class molecules. This model is supported by structure-based mutagenesis and by differential requirements for ligand oligomerization by the two subclasses in cell-based Eph receptor activation assays. Finally, the structure of the unligated receptor reveals a homodimer assembly that might represent EphA2-specific homotypic cell adhesion interactions.

PubMed: 19525919
DOI: 10.1038/embor.2009.91

実験手法

X-RAY DIFFRACTION (2.52 Å)