1. Cryo-EM structure of the CDK2-cyclin A-CDC25A complex
- Author
-
Rhianna J. Rowland, Svitlana Korolchuk, Marco Salamina, Natalie J. Tatum, James R. Ault, Sam Hart, Johan P. Turkenburg, James N. Blaza, Martin E. M. Noble, and Jane A. Endicott
- Subjects
Science - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF