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TitleStructural basis of the cyclin Y/14-3-3 protein-mediated activation of CDK16.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateMar 20, 2026
AuthorsKlara Kohoutova / Dalibor Kosek / Adam Brzezina / Karolina Honzejkova / Veronika Obsilova / Tomas Obsil /
PubMed AbstractCyclin-dependent protein kinase 16 (CDK16) regulates both physiological and pathological processes, including autophagy, spermatogenesis and cancer. Unlike other CDKs, CDK16 is regulated by an ...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.
External linksNat Commun / PubMed:41857027 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 3.83 Å
Structure data

53531

9r2i

EMDB-53531, PDB-9r2i:
Cryo-EM structure of the complex CDK16:CCNY:14-3-3
Method: EM (single particle) / Resolution: 3.3 Å

53533

9r2n

EMDB-53533, PDB-9r2n:
Cryo-EM structure of the complex CCNY:14-3-3
Method: EM (single particle) / Resolution: 3.83 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
KeywordsCYTOSOLIC PROTEIN / Kinase / Phosphorylation / Cell signalling / Cryo-EM

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