ArticleJournal of the American Society for Mass Spectrometry2019
Native Top-Down Mass Spectrometry and Ion Mobility Spectrometry of the Interaction of Tau Protein with a Molecular Tweezer Assembly Modulator.
Article in Journal of the American Society for Mass Spectrometry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Lysine-Targeting Inhibitors of Amyloidogenic Protein Aggregation: A Promise for Neurodegenerative Proteinopathies.JACS Au · 2025Review
- Mass spectrometry structural analysis of intrinsically disordered phosphoproteins.International journal of mass spectrometry · 2025Article
- Dissecting Hidden Liraglutide Oligomerization Pathways via Direct Mass Technology, Electron-Capture Dissociation, and Molecular Dynamics.Analytical chemistry · 2025Article
- A Conformation-Specific Approach to Native Top-down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024Article
- Pilot Study for Deciphering Post-Translational Modifications and Proteoforms of Tau Protein by Capillary Electrophoresis-Mass Spectrometry.Journal of proteome research · 2024Article
- Unraveling the Structure and Dynamics of Ac-PHF6-NHACS chemical neuroscience · 2024Article
- Water Plays Key Roles in Stabilities of Wild Type and Mutant Transthyretin Complexes.Journal of the American Society for Mass Spectrometry · 2024Article
- Mass spectrometry-intensive top-down proteomics: an update on technology advancements and biomedical applications.Analytical methods : advancing methods and applications · 2024Review
- Tracking Inhibition of Human Small C-Terminal Domain Phosphatase 1 Using 193 nm Ultraviolet Photodissociation Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024Article
- Panda-UV Unlocks Deeper Protein Characterization with Internal Fragments in Ultraviolet Photodissociation Mass Spectrometry.Analytical chemistry · 2024Article
- Top-down proteomics.Nature reviews. Methods primers · 2024Article
- Characterization of Molecular Tweezer Binding on α-Synuclein with Native Top-Down Mass Spectrometry and Ion Mobility-Mass Spectrometry Reveals a Mechanism for Aggregation Inhibition.Journal of the American Society for Mass Spectrometry · 2023Article
- Considerations for defining +80 Da mass shifts in mass spectrometry-based proteomics: phosphorylation and beyond.Chemical communications (Cambridge, England) · 2023Review
- Digital Quadrupole Isolation and Electron Capture Dissociation on an Extended Mass Range Q-TOF Provides Sequence and Structure Information on Proteins and Protein Complexes.Journal of the American Society for Mass Spectrometry · 2023Article
- Dissecting the structural heterogeneity of proteins by native mass spectrometry.Protein science : a publication of the Protein Society · 2023Review
- Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.Pharmacological reviews · 2023Review
- Native Top-Down Mass Spectrometry with Collisionally Activated Dissociation Yields Higher-Order Structure Information for Protein Complexes.Journal of the American Chemical Society · 2022Article
- Mass Spectrometry Methods for Measuring Protein Stability.Chemical reviews · 2022Review
- Three-repeat and four-repeat tau isoforms form different oligomers.Protein science : a publication of the Protein Society · 2022Article
- Novel Strategies to Address the Challenges in Top-Down Proteomics.Journal of the American Society for Mass Spectrometry · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
Native top-down mass spectrometry (MS) and ion mobility spectrometry (IMS) were applied to characterize the interaction of a molecular tweezer assembly modulator, CLR01, with tau, a protein believed to be involved in a number of neurodegenerative disorders, including Alzheimer's disease. The tweezer CLR01 has been shown to inhibit aggregation of amyloidogenic polypeptides without toxic side effects. ESI-MS spectra for different forms of tau protein (full-length, fragments, phosphorylated, etc.) in the presence of CLR01 indicate a primary binding stoichiometry of 1:1. The relatively high charging of the protein measured from non-denaturing solutions is typical of intrinsically disordered proteins, such as tau. Top-down mass spectrometry using electron capture dissociation (ECD) is a tool used to determine not only the sites of post-translational modifications but also the binding site(s) of non-covalent interacting ligands to biomolecules. The intact protein and the protein-modulator complex were subjected to ECD-MS to obtain sequence information, map phosphorylation sites, and pinpoint the sites of inhibitor binding. The ESI-MS study of intact tau proteins indicates that top-down MS is amenable to the study of various tau isoforms and their post-translational modifications (PTMs). The ECD-MS data point to a CLR01 binding site in the microtubule-binding region of tau, spanning residues K294-K331, which includes a six-residue nucleating segment PHF6 (VQIVYK) implicated in aggregation. Furthermore, ion mobility experiments on the tau fragment in the presence of CLR01 and phosphorylated tau reveal a shift towards a more compact structure. The mass spectrometry study suggests a picture for the molecular mechanism of the modulation of protein-protein interactions in tau by CLR01. Graphical Abstract ᅟ.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.