ArticleJournal of the American Chemical Society2020
Effects of Glutamate Arginylation on α-Synuclein: Studying an Unusual Post-Translational Modification through Semisynthesis.
Article in Journal of the American Chemical Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Genetic Code Expansion, Enzymatic Modification, and C-Terminal Labeling Enable Facile Production of Highly Modified α-Synuclein.bioRxiv : the preprint server for biology · 2026Article
- Reconstitution of protein arginylation pathways in bacteria for robust identification and quantification.Communications biology · 2026Article
- Review
- Interactions of Neurodegenerative Disease Positron Emission Tomography Imaging Probe Candidates with the C-Terminus of α-Synuclein Fibrils.Chembiochem : a European journal of chemical biology · 2025Article
- Advances in the chemical synthesis of human proteoforms.Science China. Life sciences · 2025Review
- Investigation of All Disease-Relevant Lysine Acetylation Sites in α-Synuclein Enabled by Non-canonical Amino Acid Mutagenesis.bioRxiv : the preprint server for biology · 2025Article
- Top-Down Proteomics for the Characterization and Quantification of Calreticulin Arginylation.Analytical chemistry · 2025Article
- The Search for Disease Modification in Parkinson's Disease-A Review of the Literature.Life (Basel, Switzerland) · 2025Review
- Role ofFrontiers in pharmacology · 2025Review
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- Oligomerization and a distinct tRNA-binding loop are important regulators of human arginyl-transferase function.Nature communications · 2024Article
- Combining non-canonical amino acid mutagenesis and native chemical ligation for multiply modifying proteins: A case study of α-synuclein post-translational modifications.Methods (San Diego, Calif.) · 2023Article
- Semi-Synthetic CoA-α-Synuclein Constructs Trap N-Terminal Acetyltransferase NatB for Binding Mechanism Studies.Journal of the American Chemical Society · 2023Article
- Post-translational modifications of soluble α-synuclein regulate the amplification of pathological α-synuclein.Nature neuroscience · 2023Article
- Synthesis of Peptides and Proteins with Site-Specific Glutamate Arginylation.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Effects of Mutations and Post-Translational Modifications on α-Synuclein In Vitro Aggregation.Journal of molecular biology · 2022Review
- Cysteine-Based Mimic of Arginylation Reproduces Neuroprotective Effects of the Authentic Post-Translational Modification on α-Synuclein.Journal of the American Chemical Society · 2022Article
- α-Synuclein arginylation in the human brain.Translational neurodegeneration · 2022Article
- Consequences of post-translational modifications on amyloid proteins as revealed by protein semisynthesis.Current opinion in chemical biology · 2021Review
- New strategies for fluorescently labeling proteins in the study of amyloids.Current opinion in chemical biology · 2021Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
A variety of post-translational modifications (PTMs) are believed to regulate the behavior and function of α-synuclein (αS), an intrinsically disordered protein that mediates synaptic vesicle trafficking. Fibrils of αS are implicated in neurodegenerative disorders such as Parkinson's disease. In this study, we used chemical synthesis and biophysical techniques to characterize the neuroprotective effects of glutamate arginylation, a hitherto little characterized PTM in αS. We developed semisynthetic routes combining peptide synthesis, unnatural amino acid mutagenesis, and native chemical ligation (NCL) to site-specifically introduce the PTM of interest along with fluorescent probes into αS. We synthesized the arginylated glutamate as a protected amino acid, as well as a novel ligation handle for NCL, in order to generate full-length αS modified at various individual sites or a combination of sites. We assayed the lipid-vesicle binding affinities of arginylated αS using fluorescence correlation spectroscopy (FCS) and found that arginylated αS has the same vesicle affinity compared to control protein, suggesting that this PTM does not alter the native function of αS. On the other hand, we studied the aggregation kinetics of modified αS and found that arginylation at E83, but not E46, slows aggregation and decreases the percentage incorporation of monomer into fibrils in a dose-dependent manner. Arginylation at both sites also resulted in deceleration of fibril formation. Our study represents the first synthetic strategy for incorporating glutamate arginylation into proteins and provides insight into the neuroprotective effect of this unusual PTM.
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