9R2N

Cryo-EM structure of the complex CCNY:14-3-3

Summary for 9R2N

• Entry DOI: 10.2210/pdb9r2n/pdb
• EMDB information: 53533
• Descriptor: 14-3-3 protein eta, Cyclin-Y (2 entities in total)
• Functional Keywords: kinase, phosphorylation, cell signalling, cryo-em, cytosolic protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 96817.93

Authors

Kosek, D.,Kohoutova, K.,Obsilova, V.,Obsil, T. (deposition date: 2025-04-30, release date: 2026-03-25, Last modification date: 2026-04-01)

Primary citation

Kohoutova, K.,Kosek, D.,Brzezina, A.,Honzejkova, K.,Obsilova, V.,Obsil, T.
Structural basis of the cyclin Y/14-3-3 protein-mediated activation of CDK16.
Nat Commun, 2026

PubMed Abstract: Cyclin-dependent protein kinase 16 (CDK16) regulates both physiological and pathological processes, including autophagy, spermatogenesis and cancer. Unlike other CDKs, CDK16 is regulated by an unclear mechanism involving phosphorylated cyclin Y (CCNY) in complex with 14-3-3 proteins rather than CCNY alone. The present study aims at elucidating this mechanism by structurally characterizing CDK16 in complex with CCNY and 14-3-3 using several biophysical techniques. As shown by cryo-EM analysis and hydrogen/deuterium exchange coupled to mass spectrometry, 14-3-3 binding modulates the conformation of a key moiety of the CDK binding surface of CCNY, thereby enabling CDK16 activation. CDK16 interacts with the cyclin box of CCNY, while 14-3-3 provides additional contacts, including with the activation segment of CDK16. CDK16 activation also requires interactions of CCNY with the N-terminal extension of CDK16. These findings not only clarify the role of CCNY and 14-3-3 in CDK16 activation but also highlight the potential of targeting CDK16 protein-protein interactions for cancer therapy.

PubMed: 41857027
DOI: 10.1038/s41467-026-70778-5

Experimental method

ELECTRON MICROSCOPY (3.83 Å)