9TU0

Crystal structure of human ERK1 in complex with the KIM1 motif of the T. gondii protein GRA24

9TU0 の概要

• エントリーDOI: 10.2210/pdb9tu0/pdb
• 分子名称: Mitogen-activated protein kinase 3, Putative transmembrane protein, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: phosphoryl transfer, kinase, mapk, gra24, toxoplasma, transferase
• 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: 100960.80

構造登録者

Juyoux, P.,von Velsen, J.,Bowler, M.W. (登録日: 2026-01-08, 公開日: 2026-02-25)

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

X-RAY DIFFRACTION (2.17 Å)