ArticleNature communications2016
Pharmacological chaperone reshapes the energy landscape for folding and aggregation of the prion protein.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Small Molecule Activators of Protein Phosphatase 2A Exert Global Stabilizing Effects on the Scaffold PR65.JACS Au · 2026Article
- Marginal Stability of the YB1 Cold-Shock Domain in Cells Enables Binding of Multiple Nucleic Acids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Different folding mechanisms in prion proteins from mammals with different disease susceptibility observed at the single-molecule level.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Direct observation of prion-like propagation of protein misfolding templated by pathogenic mutants.Nature chemical biology · 2024Article
- Single-molecule magnetic tweezers to probe the equilibrium dynamics of individual proteins at physiologically relevant forces and timescales.Nature protocols · 2024Review
- Single-molecule mechanical studies of chaperones and their clients.Biophysics reviews · 2022Review
- Controlling Amyloid Fibril Properties Via Ionic Liquids: The Representative Case of Ethylammonium Nitrate and Tetramethylguanidinium Acetate on the Amyloidogenesis of Lysozyme.The journal of physical chemistry letters · 2022Article
- Homodimeric complexes of the 90-231 human prion: a multilayered computational study based on FMO/GRID-DRY approach.Journal of molecular modeling · 2022Article
- Article
- Direct observation of chaperone-modulated talin mechanics with single-molecule resolution.Communications biology · 2022Article
- Co-condensation of proteins with single- and double-stranded DNA.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural dynamics of single SARS-CoV-2 pseudoknot molecules reveal topologically distinct conformers.Nature communications · 2021Article
- Asymmetric-flow field-flow fractionation of prions reveals a strain-specific continuum of quaternary structures with protease resistance developing at a hydrodynamic radius of 15 nm.PLoS pathogens · 2021Article
- Molecular Fluctuations as a Ruler of Force-Induced Protein Conformations.Nano letters · 2021Article
- Unfolded and intermediate states of PrP play a key role in the mechanism of action of an antiprion chaperone.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Acute Intermittent Porphyria: An Overview of Therapy Developments and Future Perspectives Focusing on Stabilisation of HMBS and Proteostasis Regulators.International journal of molecular sciences · 2021Review
- Visualizing and trapping transient oligomers in amyloid assembly pathways.Biophysical chemistry · 2021Review
- Optical Tweezers Approaches for Probing Multiscale Protein Mechanics and Assembly.Frontiers in molecular biosciences · 2020Review
- Structural insight into conformational change in prion protein by breakage of electrostatic network around H187 due to its protonation.Scientific reports · 2019Article
- Characterizing the inhibition of α-synuclein oligomerization by a pharmacological chaperone that prevents prion formation by the protein PrP.Protein science : a publication of the Protein Society · 2019Article
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Authors and funding
6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The development of small-molecule pharmacological chaperones as therapeutics for protein misfolding diseases has proven challenging, partly because their mechanism of action remains unclear. Here we study Fe-TMPyP, a tetrapyrrole that binds to the prion protein PrP and inhibits misfolding, examining its effects on PrP folding at the single-molecule level with force spectroscopy. Single PrP molecules are unfolded with and without Fe-TMPyP present using optical tweezers. Ligand binding to the native structure increases the unfolding force significantly and alters the transition state for unfolding, making it more brittle and raising the barrier height. Fe-TMPyP also binds the unfolded state, delaying native refolding. Furthermore, Fe-TMPyP binding blocks the formation of a stable misfolded dimer by interfering with intermolecular interactions, acting in a similar manner to some molecular chaperones. The ligand thus promotes native folding by stabilizing the native state while also suppressing interactions driving aggregation.
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