4BKA

crystal structure of the human EphA4 ectodomain in complex with human ephrin A5

4BKA の概要

• エントリーDOI: 10.2210/pdb4bka/pdb
• 関連するPDBエントリー: 4BK4 4BK5 4BKB
• 分子名称: EPHRIN TYPE-A RECEPTOR 4, EPHRIN-A5 (2 entities in total)
• 機能のキーワード: cell adhesion, cell repulsion, receptor clustering, receptor cis interaction, eph-ephrin, eph ectodomain, erythropoetin-producing hepatocellular receptor, lbd, sushi, egf, fn
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83338.93

構造登録者

Seiradake, E.,Schaupp, A.,del Toro Ruiz, D.,Kaufmann, R.,Mitakidis, N.,Harlos, K.,Aricescu, A.R.,Klein, R.,Jones, E.Y. (登録日: 2013-04-23, 公開日: 2013-07-03, 最終更新日: 2023-12-20)

主引用文献

Seiradake, E.,Schaupp, A.,Del Toro Ruiz, D.,Kaufmann, R.,Mitakidis, N.,Harlos, K.,Aricescu, A.R.,Klein, R.,Jones, E.Y.
Structurally Encoded Intraclass Differences in Epha Clusters Drive Distinct Cell Responses
Nat.Struct.Mol.Biol., 20:958-, 2013

PubMed Abstract: Functional outcomes of ephrin binding to Eph receptors (Ephs) range from cell repulsion to adhesion. Here we used cell collapse and stripe assays, showing contrasting effects of human ephrinA5 binding to EphA2 and EphA4. Despite equivalent ligand binding affinities, EphA4 triggered greater cell collapse, whereas EphA2-expressing cells adhered better to ephrinA5-coated surfaces. Chimeric receptors showed that the ectodomain is a major determinant of cell response. We report crystal structures of EphA4 ectodomain alone and in complexes with ephrinB3 and ephrinA5. These revealed closed clusters with a dimeric or circular arrangement in the crystal lattice, contrasting with extended arrays previously observed for EphA2 ectodomain. Localization microscopy showed that ligand-stimulated EphA4 induces smaller clusters than does EphA2. Mutant Ephs link these characteristics to interactions observed in the crystal lattices, suggesting a mechanism by which distinctive ectodomain surfaces determine clustering, and thereby signaling, properties.

PubMed: 23812375
DOI: 10.1038/NSMB.2617

実験手法

X-RAY DIFFRACTION (5.3 Å)