Misfolding and aggregation of transthyretin (TTR) is the basic pathophysiological mechanism of hereditary and wild type TTR amyloid (ATTR) amyloidosis. Polyneuropathy and/or cardiomyopathy with heart failure dominates the clinical presentation of the disease. Conformational changes of the TTR protein structure produce toxic intermediates that introduce cell death and ultimately loss of organ fu...

It is now widely accepted that many structurally diverse proteins can misfold and cause so-called "conformational diseases", including the most common neurodegenerations, Alzheimer's disease and Parkinson's disease. The conversion of largely a-helical or random coil proteins into cross-beta-pleated sheet conformations that form first oligomers and then fibrils underlies these disorders. However...

INTRODUCTION Pharmacological chaperone therapy (PCT) is a developing area in the treatment of diseases characterized by misfolded proteins arising from a genetic mutation. Candidates for PCT are mutant proteins that are still able to perform their function to some degree. The mutant protein must also suffer from a folding defect that causes retention in the endoplasmic reticulum (ER). Genetic m...

We present a fast method for finding optimal parameters for a low-resolution (threading) force field intended to distinguish correct from incorrect folds for a given protein sequence. In contrast to other methods, the parameterization uses information from >10(7) misfolded structures as well as a set of native sequence-structure pairs. In addition to testing the resulting force field's performa...

We examined the effects of tannin on a generalist herbivorous insect, the common cutworm (Spodoptera litura). The dosage effect was estimated by measuring the growth performance of the cutworm when the larvae were fed artificial diets containing different amounts of synthesized tannin. We used artificial diets to exclude the effects of non-tannin defense mechanisms in plant foliage. Indices of ...

Sequestration of misfolded proteins into pericentriolar inclusions called aggresomes is a means that cells use to minimize misfolded protein-induced cytotoxicity. However, the molecular mechanism by which misfolded proteins are recruited to aggresomes remains unclear. Mutations in the E3 ligase parkin cause autosomal recessive Parkinson's disease that is devoid of Lewy bodies, which are similar...

Misfolded protein aggregation in mammalian cells is one of the cellular responses to environmental stresses. However, the aggregation of misfolded proteins in plant cells exposed to environmental stresses is still poorly understood. Here, we report the misfolded protein aggregation in plant cells in response to environmental stresses, including ultraviolet (UV) radiation, heat stress and cold s...

Synonymous mutations, which alter an mRNA sequence but not the encoded protein sequence, has been found to long-timescale function of proteins, including specific activity enzymes and ability proteins form oligomers. It is unknown how synonymous mutations lead such changes in structure function, why these altered structures are fixed by proteostasis machinery. Here, we address this gap our know...