Summary
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.
Method X-RAY DIFFRACTION
Structure factors resolution 3.2 rfactor 0.221 rfree 0.261
DPI 1.69 theoretical min: 0.68
Citations

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