3C5W

Complex between PP2A-specific methylesterase PME-1 and PP2A core enzyme

3C5W の概要

• エントリーDOI: 10.2210/pdb3c5w/pdb
• 関連するPDBエントリー: 3C5V
• 分子名称: PP2A A subunit, PP2A C subunit, PP2A-specific methylesterase PME-1, ... (4 entities in total)
• 機能のキーワード: methylesterase, phosphatase, pp2a, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm : P30153 P67775
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 95676.68

構造登録者

Xing, Y.,Li, Z.,Chen, Y.,Stock, J.,Jeffrey, P.D.,Shi, Y. (登録日: 2008-02-01, 公開日: 2008-04-15, 最終更新日: 2024-04-03)

主引用文献

Xing, Y.,Li, Z.,Chen, Y.,Stock, J.B.,Jeffrey, P.D.,Shi, Y.
Structural mechanism of demethylation and inactivation of protein phosphatase 2A.
Cell(Cambridge,Mass.), 133:154-163, 2008

PubMed Abstract: Protein phosphatase 2A (PP2A) is an important serine/threonine phosphatase that plays a role in many biological processes. Reversible carboxyl methylation of the PP2A catalytic subunit is an essential regulatory mechanism for its function. Demethylation and negative regulation of PP2A is mediated by a PP2A-specific methylesterase PME-1, which is conserved from yeast to humans. However, the underlying mechanism of PME-1 function remains enigmatic. Here we report the crystal structures of PME-1 by itself and in complex with a PP2A heterodimeric core enzyme. The structures reveal that PME-1 directly binds to the active site of PP2A and that this interaction results in the activation of PME-1 by rearranging the catalytic triad into an active conformation. Strikingly, these interactions also lead to inactivation of PP2A by evicting the manganese ions that are required for the phosphatase activity of PP2A. These observations identify a dual role of PME-1 that regulates PP2A activation, methylation, and holoenzyme assembly in cells.

PubMed: 18394995
DOI: 10.1016/j.cell.2008.02.041

実験手法

X-RAY DIFFRACTION (2.8 Å)