5ETC

Structure of inactive MAPK14 with ordered Activation Loop

5ETC の概要

• エントリーDOI: 10.2210/pdb5etc/pdb
• 分子名称: Mitogen-activated protein kinase 14, SULFATE ION (3 entities in total)
• 機能のキーワード: mapk14, inactive kinase, activation loop, mapk, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: Q16539
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41812.73

構造登録者

Kapp, U.,Pellegrini, E.,Bowler, M.W. (登録日: 2015-11-17, 公開日: 2016-01-20, 最終更新日: 2023-09-27)

主引用文献

Juyoux, P.,Galdadas, I.,Gobbo, D.,von Velsen, J.,Pelosse, M.,Tully, M.,Vadas, O.,Gervasio, F.L.,Pellegrini, E.,Bowler, M.W.
Architecture of the MKK6-p38 alpha complex defines the basis of MAPK specificity and activation.
Science, 381:1217-1225, 2023

PubMed Abstract: The mitogen-activated protein kinase (MAPK) p38α is a central component of signaling in inflammation and the immune response and is, therefore, an important drug target. Little is known about the molecular mechanism of its activation by double phosphorylation from MAPK kinases (MAP2Ks), because of the challenge of trapping a transient and dynamic heterokinase complex. We applied a multidisciplinary approach to generate a structural model of p38α in complex with its MAP2K, MKK6, and to understand the activation mechanism. Integrating cryo-electron microscopy with molecular dynamics simulations, hydrogen-deuterium exchange mass spectrometry, and experiments in cells, we demonstrate a dynamic, multistep phosphorylation mechanism, identify catalytically relevant interactions, and show that MAP2K-disordered amino termini determine pathway specificity. Our work captures a fundamental step of cell signaling: a kinase phosphorylating its downstream target kinase.

PubMed: 37708276
DOI: 10.1126/science.add7859

実験手法

X-RAY DIFFRACTION (2.422 Å)