ArticleNature communications2023
Inhibitor-3 inhibits Protein Phosphatase 1 via a metal binding dynamic protein-protein interaction.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- GWAS reveal SUBER GENE1-mediated suberization via type one phosphatases.Nature plants · 2026Article
- Steric confinement-induced emission probe for monitoring protein conformations in live cells.Communications chemistry · 2026Article
- Fuzziness in enzymatic catalysis.Current opinion in structural biology · 2025Review
- The Fascinating Intricacy of pSer/Thr-Specific Phosphatases and Their Higher-Order Complexes: Emerging Concepts.Biochemistry · 2025Review
- Comprehensive pan-cancer analysis of PPP1R3G reveals its diagnostic, prognostic, and immunotherapeutic implications.Discover oncology · 2025Article
- Combining cryo-electron microscopy (cryo-EM) with orthogonal solution state methods to define the molecular basis of the phosphoprotein phosphatase family regulation and substrate specificity.Current opinion in structural biology · 2025Review
- How proteins sense their cellular environment.Nature reviews. Molecular cell biology · 2025Article
- Toward universal models for collective interactions in biomolecular condensates.Biophysics reviews · 2025Article
- Spontaneous and chaperone-assisted metal loading in the active site of protein phosphatase-1.FEBS letters · 2024Article
- Fuzzy protein-DNA interactions and beyond: A common theme in transcription?Current opinion in structural biology · 2024Review
- A protein phosphatase 1 specificProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Updates in Alzheimer's disease: from basic research to diagnosis and therapies.Translational neurodegeneration · 2024Review
- Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- [Applications of native mass spectrometry and ultraviolet photodissociation in protein structure and interaction analysis].Se pu = Chinese journal of chromatography · 2024Review
- SDS22 coordinates the assembly of holoenzymes from nascent protein phosphatase-1.Nature communications · 2024Article
- Article
- Substrate and phosphorylation site selection by phosphoprotein phosphatases.Trends in biochemical sciences · 2023Review
- Diversity of Short Linear Interaction Motifs in SARS-CoV-2 Nucleocapsid Protein.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
To achieve substrate specificity, protein phosphate 1 (PP1) forms holoenzymes with hundreds of regulatory and inhibitory proteins. Inhibitor-3 (I3) is an ancient inhibitor of PP1 with putative roles in PP1 maturation and the regulation of PP1 activity. Here, we show that I3 residues 27-68 are necessary and sufficient for PP1 binding and inhibition. In addition to a canonical RVxF motif, which is shared by nearly all PP1 regulators and inhibitors, and a non-canonical SILK motif, I3 also binds PP1 via multiple basic residues that bind directly in the PP1 acidic substrate binding groove, an interaction that provides a blueprint for how substrates bind this groove for dephosphorylation. Unexpectedly, this interaction positions a CCC (cys-cys-cys) motif to bind directly across the PP1 active site. Using biophysical and inhibition assays, we show that the I3 CCC motif binds and inhibits PP1 in an unexpected dynamic, fuzzy manner, via transient engagement of the PP1 active site metals. Together, these data not only provide fundamental insights into the mechanisms by which IDP protein regulators of PP1 achieve inhibition, but also shows that fuzzy interactions between IDPs and their folded binding partners, in addition to enhancing binding affinity, can also directly regulate enzyme activity.
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