A5091398901- Parkinson's Disease Mechanisms and Treatments
- Peptidase Inhibition and Analysis
- Chemical Synthesis and Analysis
- Cellular transport and secretion
- Biotin and Related Studies
- Signaling Pathways in Disease
- Ubiquitin and proteasome pathways
- Click Chemistry and Applications
- Alzheimer's disease research and treatments
- Neurological disorders and treatments
- Advanced Fluorescence Microscopy Techniques
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- Nerve injury and regeneration
- Advanced Polymer Synthesis and Characterization
- Protease and Inhibitor Mechanisms
- Hereditary Neurological Disorders
- Advanced Biosensing Techniques and Applications
- Biochemical and biochemical processes
- Cholinesterase and Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Genetic Neurodegenerative Diseases
- PARP inhibition in cancer therapy
- Neurological diseases and metabolism
- Neurological Disorders and Treatments
Harvard University
2023-2024
Howard Hughes Medical Institute
2023-2024
Philadelphia University
2018-2023
University of Pennsylvania
2018-2023
California University of Pennsylvania
2023
École Normale Supérieure - PSL
2015
Sorbonne Université
2015
Institut Pasteur
2015
Centre National de la Recherche Scientifique
2015
Université Paris Sciences et Lettres
2015
This paper presents Yellow Fluorescence-Activating and absorption-Shifting Tag (Y-FAST), a small monomeric protein tag, half as large the green fluorescent protein, enabling labeling of proteins in reversible specific manner through binding activation cell-permeant nontoxic fluorogenic ligand (a so-called fluorogen). A unique fluorogen mechanism based on two spectroscopic changes, increase fluorescence quantum yield absorption red shift, provides high selectivity. Y-FAST was engineered from...
Growing evidence implicates α-synuclein aggregation as a key driver of neurodegeneration in Parkinson's disease (PD) and other neurodegenerative disorders. Herein, the molecular structural mechanisms inhibiting by novel analogs nordihydroguaiaretic acid (NDGA), phenolic dibenzenediol lignan, were explored using an array biochemical biophysical methodologies. NDGA induced modest, progressive compaction monomeric α-synuclein, preventing into amyloid-like fibrils. This conformational remodeling...
NatB is one of three major N-terminal acetyltransferase (NAT) complexes (NatA-NatC), which co-translationally acetylate the N-termini eukaryotic proteins. Its substrates account for about 21% human proteome, including well known proteins such as actin, tropomyosin, CDK2, and α-synuclein (αSyn). Human (hNatB) mediated acetylation αSyn has been demonstrated to play key roles in pathogenesis Parkinson's disease a potential therapeutic target hepatocellular carcinoma. Here we report cryo-EM...
Post-translational modifications (PTMs) impact the pathological aggregation of α-synuclein (αS), a hallmark Parkinson's disease (PD). Here, we synthesize αS phosphorylated at tyrosine 39 (pY39) through novel route using in vitro enzymatic phosphorylation fragment followed by ligation to form full-length protein. We can execute this synthesis combination with unnatural amino acid mutagenesis include two fluorescent labels for Förster resonance energy transfer (FRET) studies. determine effect...
A variety of post-translational modifications (PTMs) are believed to regulate the behavior and function α-synuclein (αS), an intrinsically disordered protein that mediates synaptic vesicle trafficking. Fibrils αS implicated in neurodegenerative disorders such as Parkinson's disease. In this study, we used chemical synthesis biophysical techniques characterize neuroprotective effects glutamate arginylation, a hitherto little characterized PTM αS. We developed semisynthetic routes combining...
Abstract Background Alpha-synuclein (α-syn) exhibits pathological misfolding in many human neurodegenerative disorders. We previously showed that α-syn is arginylated the mouse brain and lack of arginylation leads to neurodegeneration mice. Methods Here, we tested pathology using newly derived antibodies combination with Western blotting, biochemical assays, experiments live neurons. Results found was on E46 E83, two sites implicated familial cases Parkinson’s disease. The levels different...
Arginylation is an understudied post-translational modification (PTM) involving the transfer of arginine to aspartate or glutamate sidechains in a protein. Among targets this PTM α-synuclein (αS), neuronal protein involved regulating synaptic vesicles. The aggregation αS implicated neurodegenerative diseases, particularly Parkinson's disease, and arginylation has been found protect against pathological process. Arginylated studied through semisynthesis multipart native chemical ligation...
Post-translational modifications (PTMs) can affect the normal function and pathology of α-synuclein (αS), an amyloid-fibril-forming protein linked to Parkinson's disease. Phosphorylation αS Tyr39 has recently been found display a dose-dependent effect on fibril formation kinetics alter morphology fibrils. Existing methods access site-specifically phosphorylated for biochemical studies include total or semi-synthesis by native chemical ligation (NCL) as well chemoenzymatic phosphorylate...
N-terminal acetylation is a chemical modification carried out by acetyltransferases. A major member of this enzyme family, NatB, acts on much the human proteome, including α-synuclein (αS), synaptic protein that mediates vesicle trafficking. NatB αS modulates its lipid binding properties and amyloid fibril formation, which underlies role in pathogenesis Parkinson's disease. Although molecular details interaction between (hNatB) N-terminus have been resolved, whether remainder plays...
Abstract The endoplasmic reticulum (ER) is shaped by abundant, membrane curvature-generating proteins that include the REEP family member REEP5. REEP1 subfamily, consisting of REEP1-4 in mammals, differs abundance and topology from Mutations REEP2 cause Hereditary Spastic Paraplegia, but REEP1-4’s function remains enigmatic. Here we show reside a novel vesicular compartment identify features determine their localization. compromise curvature-inducing activity, including those disease,...
Abstract Protein N-terminal acetylation is predominantly a ribosome-associated modification, with NatA-E serving as the major enzymes. NatC most unusual of these enzymes, containing one Naa30 catalytic subunit and two auxiliary subunits, Naa35 Naa38; substrate specificity profile that overlaps NatE. Here, we report Cryo-EM structure S. pombe NatE/C-type bisubstrate analogue inositol hexaphosphate (IP 6 ), associated biochemistry studies. We find presence three subunits prerequisite for...
Abstract NatB is one of three major N-terminal acetyltransferase (NAT) complexes (NatA-NatC), which co-translationally acetylate the N-termini eukaryotic proteins. Its substrates account for about 21% human proteome, including well known proteins such as actin, tropomyosin, CDK2, and α-synuclein (αSyn). Human (hNatB) mediated acetylation αSyn has been demonstrated to play key roles in Parkinson’s disease pathogenesis a potential therapeutic target hepatocellular carcinoma. Here we report...
Protein N-terminal acetylation is predominantly a ribosome-associated modification, with NatA-E serving as the major enzymes. NatC most unusual of these enzymes, containing one Naa30 catalytic subunit and two auxiliary subunits, Naa35 Naa38; substrate specificity profile that overlaps NatE. Here, we report Cryo-EM structure S. pombe NatE/C-type bisubstrate analogue inositol hexaphosphate (IP6), associated biochemistry studies. We find presence three subunits prerequisite for normal activity...
N-terminal acetylation is a chemical modification carried out by acetyltransferases (NATs). A major member of this enzyme family, NatB, acts on much the human proteome, including α-synuclein (αS), synaptic protein that mediates vesicle trafficking. NatB αS modulates its lipid binding properties and amyloid fibril formation, which underlies role in pathogenesis Parkinson's disease. Although molecular details interaction between (hNatB) N-terminus have been resolved, whether remainder plays...