PDB 3N5U deposited: 2010-05-25 modified: 2010-10-27
Title Crystal structure of an Rb C-terminal peptide bound to the catalytic subunit of PP1
Authors Cecchini, M., Dick, F.A., Hirschi, A., Rubin, S.M., Schamber, M.R., Steinhardt, R.C.
Structure factors resolution 3.2 rfactor 0.221 rfree 0.261
DPI 1.69 theoretical min: 0.68

The phosphorylation state and corresponding activity of the retinoblastoma tumor suppressor protein (Rb) are modulated by a balance of kinase and phosphatase activities. Here we characterize the association of Rb with the catalytic subunit of protein phosphatase 1 (PP1c). A crystal structure identifies an enzyme docking site in the Rb C-terminal domain that is required for efficient PP1c activity toward Rb. The phosphatase docking site overlaps with the known docking site for cyclin-dependent kinase (Cdk), and PP1 competition with Cdk-cyclins for Rb binding is sufficient to retain Rb activity and block cell-cycle advancement. These results provide the first detailed molecular insights into Rb activation and establish a novel mechanism for Rb regulation in which kinase and phosphatase compete for substrate docking.

Nat.Struct.Mol.Biol. 2010 Sep; 17(9):1051-1057 doi:10.1038/nsmb.1868

Cross References
Database source Identifier Description
PubMed 20694007
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3N5U/1 3N5U 1 trimer 0 3 6 3772
3N5U/2 3N5U 2 dimer 0 2 3 1936