4I5N

Structural mechanism of trimeric PP2A holoenzyme involving PR70: insight for Cdc6 dephosphorylation

Summary for 4I5N

• Entry DOI: 10.2210/pdb4i5n/pdb
• Related: 2IE3 2NPP 3P71 4I5J 4I5K 4I5L
• Related PRD ID: PRD_001031
• Descriptor: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform, Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta - Cell division control protein 6 homolog chimeric construct, Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform, PP2A-alpha, ... (7 entities in total)
• Functional Keywords: ef hand, phosphatase, cdc6 (substrate), transferase-toxin complex, hydrolase-toxin complex, hydrolase/toxin
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : P30153 P67775; Nucleus : Q99741
• Total number of polymer chains: 8
• Total formula weight: 300398.55

Authors

Wlodarchak, N.,Satyshur, K.A.,Guo, F.,Xing, Y. (deposition date: 2012-11-28, release date: 2013-05-08, Last modification date: 2023-11-15)

Primary citation

Wlodarchak, N.,Guo, F.,Satyshur, K.A.,Jiang, L.,Jeffrey, P.D.,Sun, T.,Stanevich, V.,Mumby, M.C.,Xing, Y.
Structure of the Ca(2+)-dependent PP2A heterotrimer and insights into Cdc6 dephosphorylation.
Cell Res., 23:931-946, 2013

PubMed Abstract: The B″/PR72 family of protein phosphatase 2A (PP2A) is an important PP2A family involved in diverse cellular processes, and uniquely regulated by calcium binding to the regulatory subunit. The PR70 subunit in this family interacts with cell division control 6 (Cdc6), a cell cycle regulator important for control of DNA replication. Here, we report crystal structures of the isolated PR72 and the trimeric PR70 holoenzyme at a resolution of 2.1 and 2.4 Å, respectively, and in vitro characterization of Cdc6 dephosphorylation. The holoenzyme structure reveals that one of the PR70 calcium-binding motifs directly contacts the scaffold subunit, resulting in the most compact scaffold subunit conformation among all PP2A holoenzymes. PR70 also binds distinctively to the catalytic subunit near the active site, which is required for PR70 to enhance phosphatase activity toward Cdc6. Our studies provide a structural basis for unique regulation of B″/PR72 holoenzymes by calcium ions, and suggest the mechanisms for precise control of substrate specificity among PP2A holoenzymes.

PubMed: 23752926
DOI: 10.1038/cr.2013.77

Experimental method

X-RAY DIFFRACTION (2.8 Å)