A5062435944- Prion Diseases and Protein Misfolding
- Trace Elements in Health
- RNA Research and Splicing
- Neurological diseases and metabolism
- RNA regulation and disease
- Alzheimer's disease research and treatments
- Cancer-related Molecular Pathways
- Enzyme Catalysis and Immobilization
- Protein Structure and Dynamics
- RNA modifications and cancer
- Microbial Metabolic Engineering and Bioproduction
- Parkinson's Disease Mechanisms and Treatments
- Enzyme Structure and Function
- Cholinesterase and Neurodegenerative Diseases
- HIV Research and Treatment
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Biochemical and biochemical processes
- Protein purification and stability
- Computational Drug Discovery Methods
- Analytical Chemistry and Chromatography
- Amino Acid Enzymes and Metabolism
- Enzyme-mediated dye degradation
- Biochemical Acid Research Studies
- Ubiquitin and proteasome pathways
Universidade Federal do Rio de Janeiro
2016-2025
National Institutes of Health
2020
Yale University
2020
Harvard University
2020
Rockefeller University
2020
Universidade do Estado do Rio de Janeiro
2011-2017
Centro Universitário da Cidade
2014
National Institute of Science and Technology for Structural Biology and Bioimaging
2009-2014
National Institute of Allergy and Infectious Diseases
2006
Ludwig-Maximilians-Universität München
2003
The main hypothesis for prion diseases proposes that the cellular protein (PrP(C)) can be altered into a misfolded, beta-sheet-rich isoform (PrP(Sc)), which in most cases undergoes aggregation. In an organism infected with PrP(Sc), PrP(C) is converted beta-sheet form, generating more PrP(Sc). We find sequence-specific DNA binding to recombinant murine (mPrP-(23-231)) converts it from alpha-helical conformation (cellular isoform) soluble, similar found fibrillar state. and domains bind high...
Mutant p53 tends to form aggregates with amyloid properties, especially oligomers inside the nucleus, which are believed cause oncogenic gain-of-function (GoF).
Alzheimer's disease, Parkinson's cystic fibrosis, prion diseases, and many types of cancer are considered to be protein conformation diseases. Most them also known as amyloidogenic diseases due the occurrence pathological accumulation insoluble aggregates with fibrillar conformation. Some neuroblastomas, carcinomas, myelomas show an abnormal wild-type tumor suppressor p53 either in cytoplasm or nucleus cell. Here we that core domain (p53C) can form after mild perturbation. Gentle...
Structural conversion of cellular prion protein (PrPC) into scrapie PrP (PrPSc) and subsequent aggregation are key events associated with the onset transmissible spongiform encephalopathies (TSEs). Experimental evidence supports role nucleic acids (NAs) in assisting this conversion. Here, we asked whether undergoes liquid-liquid phase separation (LLPS) if process is modulated by NAs. To end, two 25-mer DNA aptamers, A1 A2, were selected against globular domain recombinant murine (rPrP90-231)...
Prion diseases are characterized by prion protein (PrP) transmissible aggregation and neurodegeneration, which has been linked to oxidative stress. The physiological function of PrP seems related sequestering redox-active Cu 2+ , dyshomeostasis is observed in disease brain. It unclear whether contributes aggregation, recently shown be mediated condensation. This study indicates that promotes condensation live cells at the cell surface vitro through copartitioning. Molecularly, inhibited...
The main hypothesis for prion diseases proposes that the cellular protein (PrP(C)) can be altered into a misfolded, beta-sheet-rich isoform (PrP(Sc)), which undergoes aggregation and triggers onset of transmissible spongiform encephalopathies. Here, we compare stability against pressure thermomechanical properties alpha-helical beta-sheet conformations recombinant murine protein, designated as alpha-rPrP beta-rPrP, respectively. High temperature induces aggregates large gain in...
Conversion of the cellular prion protein (PrP(C)) into its altered conformation, PrP(Sc), is believed to be major cause diseases. Although PrP only identified agent for these diseases, there increasing evidence that other molecules can modulate conversion. We have found interaction with double-stranded DNA leads a higher beta-sheet content and characteristics similar those PrP(Sc). RNA also interact potentially PrP(C) PrP(Sc) conversion or even bind differentially both isoforms. Here, we...
The conversion of the prion protein (PrP) into scrapie PrP (PrPSc) is a central event in diseases. Several molecules work as cofactors process, including glycosaminoglycans (GAGs). GAGs exhibit paradoxical effect, they convert protease-resistant (PrP-res) but also exert protective activity. We compared stability and aggregation propensity heparin-PrP complex through application different vitro approaches, real-time quaking-induced (RT-QuIC). Transmissible spongiform encephalopathy–associated...
A molecular hallmark in Parkinson's disease (PD) pathogenesis are α-synuclein aggregates. Cerebral dopamine neurotrophic factor (CDNF) is an atypical growth that mostly resident the endoplasmic reticulum but exerts its effects both intracellularly and extracellularly. One of beneficial CDNF can be protecting neurons from toxic α-synuclein. Here, we investigated on aggregation vitro vivo. We found directly interacts with a KD = 23 ± 6 nM reduces auto-association. Using nuclear magnetic...
The infectious agent of transmissible spongiform encephalopathies (TSE) is believed to comprise, at least in part, the prion protein (PrP). Other molecules can modulate conversion normal PrPC into pathological conformer (PrPSc), but identity and mechanisms action key physiological factors remain unclear. PrP bind nucleic acids with relatively high affinity. Here, we report small-angle X-ray scattering (SAXS) nuclear magnetic resonance spectroscopy measurements tight complex an 18 bp DNA...
The tumor suppressor protein p53 is a nuclear that serves as an important transcription factor. region responsible for sequence-specific DNA interaction located in its core domain (p53C). Although full-length binds to tetramer, p53C monomer since it lacks the oligomerization domain. It has been previously demonstrated two domains have dimerization interface and undergo conformational change when bound DNA. Here we demonstrate with consensus sequence provides of enhanced stability at...
p53 is a transcription factor that maintains genome integrity, and its function lost in 50% of human cancers. The majority mutations are clustered within the core domain. Here, we investigate effects low pH on structure wild-type (wt) domain (p53C) R248Q mutant. At pH, tryptophan residue partially exposed to solvent, suggesting fluctuating tertiary structure. On other hand, secondary increases, as determined by circular dichroism. Binding probe bis-ANS (bis-8-anilinonaphthalene-1-sulfonate)...
The conversion of cellular prion protein (PrPC) into the pathological conformer PrPSc requires contact between both isoforms and probably also a factor, such as nucleic acid or glycosaminoglycan (GAG). Little is known about structural features implicit in GAG−PrP interaction. In present work, light scattering, fluorescence, circular dichroism, nuclear magnetic resonance (NMR) spectroscopy were used to describe chemical physical properties murine recombinant PrP 23-231 interaction with low...
A misfolded form of the prion protein (PrP) is primary culprit in mammalian diseases. It has been shown that nucleic acids catalyze misfolding cellular PrP into a scrapie-like conformer. also observed interaction with nonspecific and complex can be toxic to cultured cells. No direct correlation yet drawn between changes structure toxicity due acid binding. Here we asked whether different aggregation, stability, effects are detected when nonrelated DNA sequences interact recombinant PrP....