4IZ7

Structure of Non-Phosphorylated ERK2 bound to the PEA-15 Death Effector Domain

4IZ7 の概要

• エントリーDOI: 10.2210/pdb4iz7/pdb
• 関連するPDBエントリー: 4IZ5 4IZA
• 分子名称: Mitogen-activated protein kinase 1, Astrocytic phosphoprotein PEA-15, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: map kinase, death effector domain, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton, spindle (By similarity): P28482; Cytoplasm: Q9Z297
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 93457.90

構造登録者

Mace, P.D.,Robinson, H.,Riedl, S.J. (登録日: 2013-01-29, 公開日: 2013-04-10, 最終更新日: 2024-02-28)

主引用文献

Mace, P.D.,Wallez, Y.,Egger, M.F.,Dobaczewska, M.K.,Robinson, H.,Pasquale, E.B.,Riedl, S.J.
Structure of ERK2 bound to PEA-15 reveals a mechanism for rapid release of activated MAPK.
Nat Commun, 4:1681-1681, 2013

PubMed Abstract: ERK1/2 kinases are the principal effectors of a central signalling cascade that converts extracellular stimuli into cell proliferation and migration responses and, when deregulated, can promote cell oncogenic transformation. The scaffolding protein PEA-15 is a death effector domain protein that directly interacts with ERK1/2 and affects ERK1/2 subcellular localization and phosphorylation. Here, to understand this ERK1/2 signalling complex, we have solved the crystal structures of PEA-15 bound to three different ERK2 phospho-conformers. The structures reveal that PEA-15 uses a bipartite binding mode, occupying two key docking sites of ERK2. Remarkably, PEA-15 can efficiently bind the ERK2 activation loop in the critical Thr-X-Tyr region in different phosphorylation states. PEA-15 binding triggers an extended allosteric conduit in dually phosphorylated ERK2, disrupting key features of active ERK2. At the same time PEA-15 binding protects ERK2 from dephosphorylation, thus setting the stage for immediate ERK activity upon its release from the PEA-15 inhibitory complex.

PubMed: 23575685
DOI: 10.1038/ncomms2687

実験手法

X-RAY DIFFRACTION (1.8 Å)