3DW8

Structure of a Protein Phosphatase 2A Holoenzyme with B55 subunit

3DW8 の概要

• エントリーDOI: 10.2210/pdb3dw8/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000212
• 分子名称: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform, Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform, Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform, ... (5 entities in total)
• 機能のキーワード: holoenzyme, b55, pr55, wd repeat, hydrolase, iron, manganese, metal-binding, methylation, phosphoprotein, protein phosphatase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Cytoplasm (By similarity): P30153; Cytoplasm: P67775
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 306541.98

構造登録者

Xu, Y.,Chen, Y.,Zhang, P.,Jeffrey, P.D.,Shi, Y. (登録日: 2008-07-21, 公開日: 2008-10-07, 最終更新日: 2024-04-03)

主引用文献

Xu, Y.,Chen, Y.,Zhang, P.,Jeffrey, P.D.,Shi, Y.
Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation.
Mol.Cell, 31:873-885, 2008

PubMed Abstract: Protein phosphatase 2A (PP2A) regulates many essential aspects of cellular physiology. Members of the regulatory B/B55/PR55 family are thought to play a key role in the dephosphorylation of Tau, whose hyperphosphorylation contributes to Alzheimer's disease. The underlying mechanisms of the PP2A-Tau connection remain largely enigmatic. Here, we report the complete reconstitution of a Tau dephosphorylation assay and the crystal structure of a heterotrimeric PP2A holoenzyme involving the regulatory subunit Balpha. We show that Balpha specifically and markedly facilitates dephosphorylation of the phosphorylated Tau in our reconstituted assay. The Balpha subunit comprises a seven-bladed beta propeller, with an acidic, substrate-binding groove located in the center of the propeller. The beta propeller latches onto the ridge of the PP2A scaffold subunit with the help of a protruding beta hairpin arm. Structure-guided mutagenesis studies revealed the underpinnings of PP2A-mediated dephosphorylation of Tau.

PubMed: 18922469
DOI: 10.1016/j.molcel.2008.08.006

実験手法

X-RAY DIFFRACTION (2.85 Å)