6obr
From Proteopedia
PP1 Y134A in complex with Microcystin LR
Structural highlights
FunctionPP1A_HUMAN Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development.[1] Publication Abstract from PubMedThe 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. SDS22 selectively recognizes and traps metal-deficient inactive PP1.,Choy MS, Moon TM, Ravindran R, Bray JA, Robinson LC, Archuleta TL, Shi W, Peti W, Tatchell K, Page R Proc Natl Acad Sci U S A. 2019 Sep 23. pii: 1908718116. doi:, 10.1073/pnas.1908718116. PMID:31548429[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Microcystis aeruginosa | Archuleta TL | Bray JA | Choy MS | Moon TM | Page R | Peti W | Shi W
