9CB3

E2F1-Cyclin F Interface

Summary for 9CB3

• Entry DOI: 10.2210/pdb9cb3/pdb
• EMDB information: 45413
• Descriptor: Cyclin-F, S-phase kinase-associated protein 1, E2F1 peptide (3 entities in total)
• Functional Keywords: scf ubiquitin ligase, cell cycle
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 91916.76

Authors

Ngoi, P.,Serrao, V.H.,Rubin, S.M. (deposition date: 2024-06-18, release date: 2025-02-12, Last modification date: 2025-07-09)

Primary citation

Ngoi, P.,Wang, X.,Putta, S.,Da Luz, R.F.,Serrao, V.H.B.,Emanuele, M.J.,Rubin, S.M.
Structural mechanism for the recognition of E2F1 by the ubiquitin ligase adaptor Cyclin F.
Proc.Natl.Acad.Sci.USA, 122:e2501057122-e2501057122, 2025

PubMed Abstract: Cyclin F, a noncanonical member of the cyclin protein family, plays a critical role in regulating transitions in the cell division cycle. Unlike canonical cyclins, which bind and activate cyclin-dependent kinases (CDKs), Cyclin F functions as a substrate receptor protein within the Skp1-Cullin-F-box E3 ubiquitin ligase complex, enabling the ubiquitylation of target proteins. The structural features that distinguish Cyclin F as a ligase adaptor and the mechanisms underlying its selective substrate recruitment over Cyclin A, which functions in complex with CDK2 at a similar time in the cell cycle, remain largely unexplored. We utilized single-particle cryoelectron microscopy to elucidate the structure of a Cyclin F-Skp1 complex bound to an E2F1 peptide. The structure and biochemical analysis reveal important differences in the substrate-binding site of Cyclin F compared to Cyclin A. Our findings expand on the canonical cyclin-binding motif (Cy or RxL) and highlight the importance of electrostatics at the E2F1 binding interface, which varies between Cyclin F and Cyclin A. These results advance our understanding of E2F1 regulation and may inform strategies for selectively targeting Cyclin F in cancer or neurodegeneration.

PubMed: 40549918
DOI: 10.1073/pnas.2501057122

Experimental method

ELECTRON MICROSCOPY (3.47 Å)