A5011026810- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- Trace Elements in Health
- Amyotrophic Lateral Sclerosis Research
- RNA regulation and disease
- Protein Structure and Dynamics
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Enzyme Structure and Function
- Genetic Neurodegenerative Diseases
- Genomics and Chromatin Dynamics
- Heat shock proteins research
- Mitochondrial Function and Pathology
- Microbial Metabolic Engineering and Bioproduction
- Fungal and yeast genetics research
- Wnt/β-catenin signaling in development and cancer
- Advanced NMR Techniques and Applications
- Skin and Cellular Biology Research
- RNA and protein synthesis mechanisms
- Amino Acid Enzymes and Metabolism
- Fibroblast Growth Factor Research
- Quantum, superfluid, helium dynamics
- Peptidase Inhibition and Analysis
Uniformed Services University of the Health Sciences
2011-2021
California University of Pennsylvania
2020
Regenerative Medicine Institute
2015
National Institute of Diabetes and Digestive and Kidney Diseases
2004-2010
National Institutes of Health
2004-2010
Pediatrics and Genetics
2009
Tulane University
2001-2004
University of Geneva
2004
Auburn University
1998
Article8 August 2017Open Access Transparent process Phosphorylation of the FUS low-complexity domain disrupts phase separation, aggregation, and toxicity Zachary Monahan Department Pharmacology Molecular Therapeutics, Uniformed Services University, Bethesda, MD, USA Search for more papers by this author Veronica H Ryan Neuroscience Graduate Program, Brown Providence, RI, Abigail M Janke Pharmacology, Physiology, Biotechnology, Kathleen A Burke Shannon N Rhoads Gül Zerze Chemical Biomolecular...
Article9 February 2018Open Access Transparent process A single N-terminal phosphomimic disrupts TDP-43 polymerization, phase separation, and RNA splicing Ailin Wang Department of Molecular Pharmacology, Physiology, Biotechnology, Brown University, Providence, RI, USA Search for more papers by this author Alexander E Conicella Graduate Program in Biology, Cell Biology Biochemistry, Hermann Broder Schmidt Stanford University School Medicine, Stanford, CA, Erik W Martin Structural St. Jude...
The [PSI(+)] prion of Saccharomyces cerevisiae is a self-propagating amyloid form Sup35p, subunit the translation termination factor. Using solid-state NMR we have examined structure fibrils formed in vitro from purified recombinant Sup35(1-253), consisting glutamine- and asparagine-rich N-terminal 123-residue domain (N) adjacent 130-residue highly charged M domain. Measurements magnetic dipole-dipole couplings among (13)C nuclei series Sup35NM fibril samples, (13)C-labeled at backbone...
Amyotrophic lateral sclerosis (ALS) is an uncommon neurodegenerative disease caused by degeneration of upper and lower motor neurons. Several genes, including SOD1, TDP-43, FUS, Ubiquilin 2, C9orf72 Profilin 1, have been linked with the sporadic familiar forms ALS. FUS a DNA/RNA-binding protein (RBP) that cytoplasmic inclusions in ALS frontotemporal lobular (FTLD) patients' brains spinal cords. However, it unknown whether RNA-binding ability required for causing pathogenesis. Here, we...
Pmel17 is a melanocyte protein necessary for eumelanin deposition 1 in mammals and found melanosomes filamentous form. The luminal part of human includes region (RPT) with 10 copies partial repeat sequence, pt.e.gttp.qv., known to be essential vivo filament formation. We show that this RPT readily forms amyloid vitro, but only under the mildly acidic conditions typical lysosome-like melanosome lumen, filaments quickly become soluble at neutral pH. Under same conditions, Pmel promote Electron...
We demonstrate that accurate values of mass-per-length (MPL), which serve as strong constraints on molecular structure, can be determined for amyloid fibrils by quantification intensities in dark-field electron microscope images obtained the tilted-beam mode a transmission microscope. MPL formed residues 218-289 HET-s fungal prion protein, 2-fold- and 3-fold-symmetric 40-residue beta-amyloid peptide, yeast protein Sup35NM are good agreement with previous results from scanning microscopy....
The extracellular curli proteins of Enterobacteriaceae form fibrous structures that are involved in biofilm formation and adhesion to host cells. These fibrils considered a functional amyloid because they not consequence misfolding, but have many the properties protein amyloid. We confirm formed by CsgA CsgB, primary Escherichia coli, possess hallmarks typical Moreover we demonstrate cross-beta structure distinguishes However, solid state NMR experiments indicate is based on an in-register...
ABSTRACT Myxoid liposarcoma is caused by a chromosomal translocation resulting in fusion protein comprised of the N terminus FUS (fused sarcoma) and full-length transcription factor CHOP (CCAAT/enhancer-binding homologous protein, also known as DDIT3). functions RNA metabolism, stress-induced factor. The FUS-CHOP causes unique gene expression oncogenic transformation. Although it clear that segment required for transformation, mechanism FUS-CHOP-induced transcriptional activation unknown....
The [PSI(+)] prion is a self-propagating amyloid of the Sup35 protein, normally subunit translation termination factor, but impaired in this vital function when form. N, M, and C domains are amino-terminal domain, connecting polar essential C-terminal domain resembling eukaryotic elongation factor 1alpha respectively. Different isolates (prion variants) may have distinct biological properties, associated with different structures. Here we use solid state NMR to examine structure infectious...
Many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) are linked to the accumulation of specific protein aggregates in affected regions nervous system. SOD1, TDP-43, FUS and optineurin (OPTN) proteins were identified form intraneuronal inclusions ALS patients. In addition, mutations OPTN associated with both glaucoma. As pathological role neuronal degeneration remains unresolved, we created a yeast model study its potential for aggregation toxicity. We observed that...
Even deadly prions may be widespread in nature if they spread by infection faster than kill off their hosts. The yeast [PSI+] and [URE3] (amyloids of Sup35p Ure2p) were not found 70 wild strains, while [PIN+] (amyloid Rnq1p) was ∼16% the same population. Yeast prion occurs only mating, balancing detrimental effects carrying prion. We estimated frequency outcross mating as about 1% mitotic doublings from known detriment 2-μm DNA plasmid (∼1%) its populations (38/70). also fraction total...
FUS (fused in sarcoma) is an abundant, predominantly nuclear protein involved RNA processing. Under various conditions, functionally associates with and other macromolecules to form distinct, reversible phase-separated liquid structures. Persistence of the state increased cytoplasmic localization are both hypothesized predispose irreversible aggregation, which a pathological hallmark subtypes amyotrophic lateral sclerosis frontotemporal dementia. We previously showed that phosphorylation...