8ROZ

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

8ROZ の概要

• エントリーDOI: 10.2210/pdb8roz/pdb
• EMDBエントリー: 19408
• 分子名称: Cyclin-dependent kinase 2, Cyclin-A2, M-phase inducer phosphatase 1 (3 entities in total)
• 機能のキーワード: cell-cycle, cdk, phosphatase, cancer, cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 86789.37

構造登録者

Rowland, R.J.,Noble, M.E.M.,Endicott, J.A. (登録日: 2024-01-12, 公開日: 2024-05-29, 最終更新日: 2024-08-28)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.7 Å)