4V0V

The crystal structure of mouse PP1G in complex with truncated human PPP1R15B (631-660)

4V0V の概要

• エントリーDOI: 10.2210/pdb4v0v/pdb
• 関連するPDBエントリー: 4V0U 4V0W 4V0X
• 分子名称: SERINE/THREONINE-PROTEIN PHOSPHATASE PP1-GAMMA CATALYTIC SUBUNIT, PROTEIN PHOSPHATASE 1 REGULATORY SUBUNIT 15B, MANGANESE (II) ION, ... (5 entities in total)
• 機能のキーワード: hydrolase-hydrolase regulator complex, hydrolase/hydrolase regulator
• 由来する生物種: MUS MUSCULUS (HOUSE MOUSE); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 76117.01

構造登録者

Chen, R.,Yan, Y.,Casado, A.C.,Ron, D.,Read, R.J. (登録日: 2014-09-18, 公開日: 2015-03-25, 最終更新日: 2024-01-10)

主引用文献

Chen, R.,Rato, C.,Yan, Y.,Crespillo-Casado, A.,Clarke, H.J.,Harding, H.P.,Marciniak, S.J.,Read, R.J.,Ron, D.
G-actin provides substrate-specificity to eukaryotic initiation factor 2 alpha holophosphatases.
Elife, 4:-, 2015

PubMed Abstract: Dephosphorylation of eukaryotic translation initiation factor 2a (eIF2a) restores protein synthesis at the waning of stress responses and requires a PP1 catalytic subunit and a regulatory subunit, PPP1R15A/GADD34 or PPP1R15B/CReP. Surprisingly, PPP1R15-PP1 binary complexes reconstituted in vitro lacked substrate selectivity. However, selectivity was restored by crude cell lysate or purified G-actin, which joined PPP1R15-PP1 to form a stable ternary complex. In crystal structures of the non-selective PPP1R15B-PP1G complex, the functional core of PPP1R15 made multiple surface contacts with PP1G, but at a distance from the active site, whereas in the substrate-selective ternary complex, actin contributes to one face of a platform encompassing the active site. Computational docking of the N-terminal lobe of eIF2a at this platform placed phosphorylated serine 51 near the active site. Mutagenesis of predicted surface-contacting residues enfeebled dephosphorylation, suggesting that avidity for the substrate plays an important role in imparting specificity on the PPP1R15B-PP1G-actin ternary complex.

PubMed: 25774600
DOI: 10.7554/eLife.04871

実験手法

X-RAY DIFFRACTION (1.61 Å)