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Eukaryotic cells contain assemblies of RNAs and proteins termed RNA granules. Many proteins within these bodies contain KH or RRM RNA-binding domains as well as low complexity (LC) sequences of unknown function. We discovered that exposure of cell or tissue lysates to a biotinylated isoxazole (b-isox) chemical precipitated hundreds of RNA-binding proteins(More)
We present a structural model for amyloid fibrils formed by the 40-residue beta-amyloid peptide associated with Alzheimer's disease (Abeta(1-40)), based on a set of experimental constraints from solid state NMR spectroscopy. The model additionally incorporates the cross-beta structural motif established by x-ray fiber diffraction and satisfies constraints(More)
In vitro, β-amyloid (Aβ) peptides form polymorphic fibrils, with molecular structures that depend on growth conditions, plus various oligomeric and protofibrillar aggregates. Here, we investigate structures of human brain-derived Aβ fibrils, using seeded fibril growth from brain extract and data from solid-state nuclear magnetic resonance and electron(More)
Education (fellowship to ONA), the Japan Society for the Promotion of Science (fellowship to YI), and the Whitaker Foundation through the NIH Biomedical Engineering Summer Internship Program (internship to JR). Solid state NMR techniques used in this work were developed under grants to RT from the NIH Intramural AIDS Targeted Antiviral Program. Abstract The(More)
Amyloid fibrils commonly exhibit multiple distinct morphologies in electron microscope and atomic force microscope images, often within a single image field. By using electron microscopy and solid-state nuclear magnetic resonance measurements on fibrils formed by the 40-residue beta-amyloid peptide of Alzheimer's disease (Abeta(1-40)), we show that(More)
Filamentous amyloid aggregates are central to the pathology of Alzheimer's disease. We use all-atom molecular dynamics (MD) simulations with explicit solvent and multiple force fields to probe the structural stability and the conformational dynamics of several models of Alzheimer's beta-amyloid fibril structures, for both wild-type and mutated amino acid(More)
The wild-type HIV-1 capsid protein (CA) self-assembles in vitro into tubular structures at high ionic strength. We report solid state nuclear magnetic resonance (NMR) and electron microscopy measurements on these tubular CA assemblies, which are believed to contain a triangular lattice of hexameric CA proteins that is similar or identical to the lattice of(More)
The [URE3] and [PSI (+)] prions of Saccharomyces cerevisiae are self-propagating amyloid forms of Ure2p and Sup35p, respectively. The Q/N-rich N-terminal domains of each protein are necessary and sufficient for the prion properties of these proteins, forming in each case their amyloid cores. Surprisingly, shuffling either prion domain, leaving amino acid(More)
Aggregation of amyloid-β peptides into fibrils or other self-assembled states is central to the pathogenesis of Alzheimer's disease. Fibrils formed in vitro by 40- and 42-residue amyloid-β peptides (Aβ40 and Aβ42) are polymorphic, with variations in molecular structure that depend on fibril growth conditions. Recent experiments suggest that variations in(More)