Structure of the Ca2＋-dependent PP2A heterotrimer and insights into Cdc6 dephosphorylation

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 in- teracts with cell division control 6 （Cdc6）, a cell cycle regulator importa...

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Bibliographic Details
Published in:Cell research 2013-07, Vol.23 (7), p.931-946
Main Authors: Wlodarchak, Nathan, Guo, Feng, Satyshur, Kenneth A, Jiang, Li, Jeffrey, Philip D, Sun, Tingwan, Stanevich, Vitali, Mumby, Marc C, Xing, Yongna
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
Cell Cycle Proteins - metabolism
Crystallography, X-Ray
Holoenzymes - chemistry
Holoenzymes - metabolism
Humans
Original
Phosphorylation
PP2A
Protein Phosphatase 2 - chemistry
Protein Phosphatase 2 - metabolism
Protein Subunits - chemistry
Protein Subunits - metabolism
Substrate Specificity
亚基相互作用
去磷酸化
异源
精确控制
细胞周期调控
解结构
钙依赖性
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Summary: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 in- teracts 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 A, re- spectively, 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 sub- strate specificity among PP2A holoenzymes.
ISSN:1001-0602
1748-7838
DOI:10.1038/cr.2013.77