6SG4

Structure of CDK2/cyclin A M246Q, S247EN

Summary for 6SG4

• Entry DOI: 10.2210/pdb6sg4/pdb
• Descriptor: Cyclin-dependent kinase 2, Cyclin-A2 (3 entities in total)
• Functional Keywords: cyclin-dependent kinases, cancer, cyclin a, cdk2, cell cycle, skp2
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 130927.16

Authors

Salamina, M.,Basle, A.,Massa, B.,Noble, M.E.M.,Endicott, J.A. (deposition date: 2019-08-02, release date: 2021-01-27, Last modification date: 2024-11-13)

Primary citation

Salamina, M.,Montefiore, B.C.,Liu, M.,Wood, D.J.,Heath, R.,Ault, J.R.,Wang, L.Z.,Korolchuk, S.,Basle, A.,Pastok, M.W.,Reeks, J.,Tatum, N.J.,Sobott, F.,Arold, S.T.,Pagano, M.,Noble, M.E.M.,Endicott, J.A.
Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation.
J.Mol.Biol., 433:166795-166795, 2021

PubMed Abstract: The SCF ubiquitin ligase relieves G1 checkpoint control of CDK-cyclin complexes by promoting p27KIP1 degradation. We describe reconstitution of stable complexes containing SKP1-SKP2 and CDK1-cyclin B or CDK2-cyclin A/E, mediated by the CDK regulatory subunit CKS1. We further show that a direct interaction between a SKP2 N-terminal motif and cyclin A can stabilize SKP1-SKP2-CDK2-cyclin A complexes in the absence of CKS1. We identify the SKP2 binding site on cyclin A and demonstrate the site is not present in cyclin B or cyclin E. This site is distinct from but overlapping with features that mediate binding of p27KIP1 and other G1 cyclin regulators to cyclin A. We propose that the capacity of SKP2 to engage with CDK2-cyclin A by more than one structural mechanism provides a way to fine tune the degradation of p27KIP1 and distinguishes cyclin A from other G1 cyclins to ensure orderly cell cycle progression.

PubMed: 33422522
DOI: 10.1016/j.jmb.2020.166795

Experimental method

X-RAY DIFFRACTION (2.43 Å)