8ROZ

Cryo-EM structure of CDK2-cyclin A in complex with CDC25A

Summary for 8ROZ

• Entry DOI: 10.2210/pdb8roz/pdb
• EMDB information: 19408
• Descriptor: Cyclin-dependent kinase 2, Cyclin-A2, M-phase inducer phosphatase 1 (3 entities in total)
• Functional Keywords: cell-cycle, cdk, phosphatase, cancer, cell cycle
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 86789.37

Authors

Rowland, R.J.,Noble, M.E.M.,Endicott, J.A. (deposition date: 2024-01-12, release date: 2024-05-29, Last modification date: 2024-08-28)

Primary citation

Rowland, R.J.,Korolchuk, S.,Salamina, M.,Tatum, N.J.,Ault, J.R.,Hart, S.,Turkenburg, J.P.,Blaza, J.N.,Noble, M.E.M.,Endicott, J.A.
Cryo-EM structure of the CDK2-cyclin A-CDC25A complex.
Nat Commun, 15:6807-6807, 2024

PubMed Abstract: The cell division cycle 25 phosphatases CDC25A, B and C regulate cell cycle transitions by dephosphorylating residues in the conserved glycine-rich loop of CDKs to activate their activity. Here, we present the cryo-EM structure of CDK2-cyclin A in complex with CDC25A at 2.7 Å resolution, providing a detailed structural analysis of the overall complex architecture and key protein-protein interactions that underpin this 86 kDa complex. We further identify a CDC25A C-terminal helix that is critical for complex formation. Sequence conservation analysis suggests CDK1/2-cyclin A, CDK1-cyclin B and CDK2/3-cyclin E are suitable binding partners for CDC25A, whilst CDK4/6-cyclin D complexes appear unlikely substrates. A comparative structural analysis of CDK-containing complexes also confirms the functional importance of the conserved CDK1/2 GDSEID motif. This structure improves our understanding of the roles of CDC25 phosphatases in CDK regulation and may inform the development of CDC25-targeting anticancer strategies.

PubMed: 39122719
DOI: 10.1038/s41467-024-51135-w

Experimental method

ELECTRON MICROSCOPY (2.7 Å)