4NIF

Heterodimeric structure of ERK2 and RSK1

4NIF の概要

• エントリーDOI: 10.2210/pdb4nif/pdb
• 分子名称: Ribosomal protein S6 kinase alpha-1, Mitogen-activated protein kinase 1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (6 entities in total)
• 機能のキーワード: kinase domain, signaling, substrate kinase binding, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q15418; Cytoplasm, cytoskeleton, spindle : P28482
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 159509.75

構造登録者

Gogl, G.,Remenyi, A. (登録日: 2013-11-06, 公開日: 2014-11-12, 最終更新日: 2023-11-08)

主引用文献

Alexa, A.,Gogl, G.,Glatz, G.,Garai, A.,Zeke, A.,Varga, J.,Dudas, E.,Jeszenoi, N.,Bodor, A.,Hetenyi, C.,Remenyi, A.
Structural assembly of the signaling competent ERK2-RSK1 heterodimeric protein kinase complex
Proc.Natl.Acad.Sci.USA, 112:2711-2716, 2015

PubMed Abstract: Mitogen-activated protein kinases (MAPKs) bind and activate their downstream kinase substrates, MAPK-activated protein kinases (MAPKAPKs). Notably, extracellular signal regulated kinase 2 (ERK2) phosphorylates ribosomal S6 kinase 1 (RSK1), which promotes cellular growth. Here, we determined the crystal structure of an RSK1 construct in complex with its activator kinase. The structure captures the kinase-kinase complex in a precatalytic state where the activation loop of the downstream kinase (RSK1) faces the enzyme's (ERK2) catalytic site. Molecular dynamics simulation was used to show how this heterodimer could shift into a signaling-competent state. This structural analysis combined with biochemical and cellular studies on MAPK→MAPKAPK signaling showed that the interaction between the MAPK binding linear motif (residing in a disordered kinase domain extension) and the ERK2 "docking" groove plays the major role in making an encounter complex. This interaction holds kinase domains proximal as they "readjust," whereas generic kinase domain surface contacts bring them into a catalytically competent state.

PubMed: 25730857
DOI: 10.1073/pnas.1417571112

実験手法

X-RAY DIFFRACTION (2.15 Å)