ArticleJournal of biomolecular NMR2013
Unraveling a phosphorylation event in a folded protein by NMR spectroscopy: phosphorylation of the Pin1 WW domain by PKA.
Article in Journal of biomolecular NMR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Dissecting the functional behavior of the differentially phosphorylated prolyl isomerase, Pin1.Protein science : a publication of the Protein Society · 2024Article
- The role of peptidyl-prolyl isomerase Pin1 in neuronal signaling in epilepsy.Frontiers in molecular neuroscience · 2022Review
- Characterizing Post-Translational Modifications and Their Effects on Protein Conformation Using NMR Spectroscopy.Biochemistry · 2020Review
- Multiple Site-Specific Phosphorylation of IDPs Monitored by NMR.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Random coil shifts of posttranslationally modified amino acids.Journal of biomolecular NMR · 2019Article
- Review
- Molecular Mechanism of the Pin1-Histone H1 Interaction.Biochemistry · 2019Article
- Direct Crosstalk BetweenFrontiers in endocrinology · 2018Article
- Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins.Journal of visualized experiments : JoVE · 2016Article
- Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome.Scientific reports · 2016Article
- NMR Meets Tau: Insights into Its Function and Pathology.Biomolecules · 2016Review
- The human Na(+)/H(+) exchanger 1 is a membrane scaffold protein for extracellular signal-regulated kinase 2.BMC biology · 2016Article
- Review
- Investigating Dynamic Interdomain Allostery in Pin1.Biophysical reviews · 2015Article
- pH-dependent random coil (1)H, (13)C, and (15)N chemical shifts of the ionizable amino acids: a guide for protein pK a measurements.Journal of biomolecular NMR · 2014Article
- The cellular peptidyl-prolyl cis/trans isomerase Pin1 regulates reactivation of Kaposi's sarcoma-associated herpesvirus from latency.Journal of virology · 2014Article
- Site-specific NMR mapping and time-resolved monitoring of serine and threonine phosphorylation in reconstituted kinase reactions and mammalian cell extracts.Nature protocols · 2013Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Pin1 protein plays a critical role in the functional regulation of the hyperphosphorylated neuronal Tau protein in Alzheimer's disease and is by itself regulated by phosphorylation. We have used Nuclear Magnetic Resonance (NMR) spectroscopy to both identify the PKA phosphorylation site in the Pin1 WW domain and investigate the functional consequences of this phosphorylation. Detection and identification of phosphorylation on serine/threonine residues in a globular protein, while mostly occurring in solvent-exposed flexible loops, does not lead to chemical shift changes as obvious as in disordered proteins and hence does not necessarily shift the resonances outside the spectrum of the folded protein. Other complications were encountered to characterize the extent of the phosphorylation, as part of the (1)H,(15)N amide resonances around the phosphorylation site are specifically broadened in the unphosphorylated state. Despite these obstacles, NMR spectroscopy was an efficient tool to confirm phosphorylation on S16 of the WW domain and to quantify the level of phosphorylation. Based on this analytical characterization, we show that WW phosphorylation on S16 abolishes its binding capacity to a phosphorylated Tau peptide. A reduced conformational heterogeneity and flexibility of the phospho-binding loop upon S16 phosphorylation could account for part of the decreased affinity for its phosphorylated partner. Additionally, a structural model of the phospho-WW obtained by molecular dynamics simulation and energy minimization suggests that the phosphate moiety of phospho-S16 could compete with the phospho-substrate.
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