2RLT

phosphorylated CPI-17 (22-120)

2RLT の概要

• エントリーDOI: 10.2210/pdb2rlt/pdb
• 関連するPDBエントリー: 1J2M 1J2N
• 分子名称: Protein phosphatase 1 regulatory subunit 14A (1 entity in total)
• 機能のキーワード: phosphorylation, pp1 inhibitor, cytoplasm, protein phosphatase inhibitor, hydrolase
• 由来する生物種: Sus scrofa (Pig)
• 細胞内の位置: Cytoplasm: O18734
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11626.06

構造登録者

Eto, M. (登録日: 2007-08-11, 公開日: 2008-07-15, 最終更新日: 2024-11-20)

主引用文献

Eto, M.,Kitazawa, T.,Matsuzawa, F.,Aikawa, S.,Kirkbride, J.A.,Isozumi, N.,Nishimura, Y.,Brautigan, D.L.,Ohki, S.Y.
Phosphorylation-induced conformational switching of CPI-17 produces a potent myosin phosphatase inhibitor.
Structure, 15:1591-1602, 2007

PubMed Abstract: Phosphorylation of endogenous inhibitor proteins for type-1 Ser/Thr phosphatase (PP1) provides a mechanism for reciprocal coordination of kinase and phosphatase activities. A myosin phosphatase inhibitor protein CPI-17 is phosphorylated at Thr38 through G-protein-mediated signals, resulting in a >1000-fold increase in inhibitory potency. We show here the solution NMR structure of phospho-T38-CPI-17 with rmsd of 0.36 +/- 0.06 A for the backbone secondary structure, which reveals how phosphorylation triggers a conformational change and exposes an inhibitory surface. This active conformation is stabilized by the formation of a hydrophobic core of intercalated side chains, which is not formed in a phospho-mimetic D38 form of CPI-17. Thus, the profound increase in potency of CPI-17 arises from phosphorylation, conformational change, and hydrophobic stabilization of a rigid structure that poses the phosphorylated residue on the protein surface and restricts its hydrolysis by myosin phosphatase. Our results provide structural insights into transduction of kinase signals by PP1 inhibitor proteins.

PubMed: 18073109
DOI: 10.1016/j.str.2007.10.014

実験手法

SOLUTION NMR