9TYG

Structure of the MAP2K MEK1 in an inactive conformation in complex with its substrate MAPK ERK2

9TYG の概要

• エントリーDOI: 10.2210/pdb9tyg/pdb
• EMDBエントリー: 56418 56419 56420
• 分子名称: Dual specificity mitogen-activated protein kinase kinase 1,Uncharacterized protein,Dual specificity mitogen-activated protein kinase kinase 1, Mitogen-activated protein kinase 1, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: protein kinases, phosphoryl transfer, mapk, map2k, cancer signaling, signaling protein
• 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: 87585.25

構造登録者

von Velsen, J.,Juyoux, P.,Bowler, M.W. (登録日: 2026-01-19, 公開日: 2026-02-11, 最終更新日: 2026-02-18)

主引用文献

von Velsen, J.,Juyoux, P.,Piasentin, N.,Fisher, H.,Lapouge, K.,Vadas, O.,Gervasio, F.L.,Bowler, M.W.
Molecular basis of mitogen-activated protein kinase ERK2 activation by its upstream kinase MEK1.
Biorxiv, 2026

PubMed Abstract: The RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) pathway relays extracellular signals into a cellular response and its dysregulation leads to many pathologies, particularly cancer. Here, we determined cryo-EM structures of the MAP2K MEK1 activating its substrate MAPK ERK2, the final event in the cascade. We define the molecular details of specificity and phosphoryl transfer to the tyrosine of the ERK2 activation loop and examine the mechanism of substrate recognition using solution techniques and molecular dynamics. Binding of the substrate MAPK leads to release of the MAP2K catalytic machinery, explaining the mechanism of many disease-causing mutations, and ERK2 release is not required for nucleotide exchange, suggesting a processive mechanism. Our data advance the understanding of MAPK signalling and provide a starting point for drug development.

PubMed: 41648251
DOI: 10.64898/2026.01.19.700303

実験手法

ELECTRON MICROSCOPY (2.9 Å)