6OBS

PP1 Y134K

6OBS の概要

• エントリーDOI: 10.2210/pdb6obs/pdb
• 分子名称: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, MANGANESE (II) ION, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: phosphatase, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68758.10

構造登録者

Choy, M.S.,Moon, T.M.,Bray, J.A.,Archuleta, T.L.,Shi, W.,Peti, W.,Page, R. (登録日: 2019-03-21, 公開日: 2019-09-18, 最終更新日: 2023-10-11)

主引用文献

Choy, M.S.,Moon, T.M.,Ravindran, R.,Bray, J.A.,Robinson, L.C.,Archuleta, T.L.,Shi, W.,Peti, W.,Tatchell, K.,Page, R.
SDS22 selectively recognizes and traps metal-deficient inactive PP1.
Proc.Natl.Acad.Sci.USA, 116:20472-20481, 2019

PubMed Abstract: The metalloenzyme protein phosphatase 1 (PP1), which is responsible for ≥50% of all dephosphorylation reactions, is regulated by scores of regulatory proteins, including the highly conserved SDS22 protein. SDS22 has numerous diverse functions, surprisingly acting as both a PP1 inhibitor and as an activator. Here, we integrate cellular, biophysical, and crystallographic studies to address this conundrum. We discovered that SDS22 selectively binds a unique conformation of PP1 that contains a single metal (M2) at its active site, i.e., SDS22 traps metal-deficient inactive PP1. Furthermore, we showed that SDS22 dissociation is accompanied by a second metal (M1) being loaded into PP1, as free metal cannot dissociate the complex and M1-deficient mutants remain constitutively trapped by SDS22. Together, our findings reveal that M1 metal loading and loss are essential for PP1 regulation in cells, which has broad implications for PP1 maturation, activity, and holoenzyme subunit exchange.

PubMed: 31548429
DOI: 10.1073/pnas.1908718116

実験手法

X-RAY DIFFRACTION (1.803 Å)