9TU0

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

Summary for 9TU0

• Entry DOI: 10.2210/pdb9tu0/pdb
• Descriptor: Mitogen-activated protein kinase 3, Putative transmembrane protein, SULFATE ION, ... (4 entities in total)
• Functional Keywords: phosphoryl transfer, kinase, mapk, gra24, toxoplasma, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 100960.80

Authors

Juyoux, P.,von Velsen, J.,Bowler, M.W. (deposition date: 2026-01-08, release date: 2026-02-25)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.17 Å)