3N5U

Crystal structure of an Rb C-terminal peptide bound to the catalytic subunit of PP1

Summary for 3N5U

• Entry DOI: 10.2210/pdb3n5u/pdb
• Descriptor: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, Retinoblastoma-associated protein, MANGANESE (II) ION, ... (4 entities in total)
• Functional Keywords: retinoblastoma, prb, rb, protein phosphatase-1, pp1, phosphatase, hydrolase, transcription regulation
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P62136; Nucleus: P06400
• Total number of polymer chains: 3
• Total formula weight: 70566.22

Authors

Hirschi, A.M.,Cecchini, M.,Steinhardt, R.C.,Dick, F.A.,Rubin, S.M. (deposition date: 2010-05-25, release date: 2010-08-11, Last modification date: 2024-02-21)

Primary citation

Hirschi, A.,Cecchini, M.,Steinhardt, R.C.,Schamber, M.R.,Dick, F.A.,Rubin, S.M.
An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein.
Nat.Struct.Mol.Biol., 17:1051-1057, 2010

PubMed Abstract: 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.

PubMed: 20694007
DOI: 10.1038/nsmb.1868

Experimental method

X-RAY DIFFRACTION (3.2 Å)