6OBP

Reconstituted PP1 holoenzyme

Summary for 6OBP

• Entry DOI: 10.2210/pdb6obp/pdb
• Descriptor: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, Protein phosphatase 1 regulatory subunit 7, PHOSPHATE ION, ... (6 entities in total)
• Functional Keywords: complex, phosphatase, holoenzyme, regulator, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 71279.41

Authors

Choy, M.S.,Moon, T.M.,Bray, J.A.,Archuleta, T.L.,Shi, W.,Peti, W.,Page, R. (deposition date: 2019-03-21, release date: 2019-09-18, Last modification date: 2023-10-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)