While agent host-range and strain properties convinced early researchers of a viral etiology, the once unorthodox postulate that prion transmission occurs by conformational corruption of hostencoded cellular prion protein (PrP) by a pathogenic isoform (PrP) is now widely accepted. Indeed, conformational templating is increasingly understood to be a general mechanism of proteinmediated informati...

The gene expression control by DNA-binding drugs is of great interest in molecular biology and biotechnology. The ability of some drugs to switch on or off the gene expression brings the possibility to develop treatments for genetic diseases, infection by antibiotic-resistant bacteria, or cancer. The analysis of the DNA sequence-dependent conformational energy gives hints for the design of DNAb...

Adenylate Kinase (AK) is a signal transducing protein that regulates cellular energy homeostasis balancing between different conformations. An alteration of its activity can lead to severe pathologies such as heart failure, cancer and neurodegenerative diseases. A comprehensive elucidation of the large-scale conformational motions that rule the functional mechanism of this enzyme is of great va...

In this paper we report on a combination of experimental and theoretical study of a new copolymer based on carbazole and methylthiophene (Cbz-Mth), in their neutral and oxidized states. We discuss the influence of chain length on conformational and optoelectronic properties with the DFT method. Conformational analysis shows that there are no big changes in the structural parameters of neutral o...

Biological systems are often exposed to mechanical perturbations, which may modulate many biochemical processes. Ligand binding involves a wide range of structural changes in the receptor protein, from hinge movement entire domains minor sidechain rearrangements pocket residues. Hydrophobic ligand protein alters system’s vibrational free energy, allowing different conformational states alloster...

Based on recent experimental evidences of the transmission of prion diseases due to a particular transmembrane form (termed (Ctm)PrP), we propose a theoretical model for the molecular mechanism of such conformational diseases, in which a misfolded (Ctm)PrP induces a similar misfolding of another (Ctm)PrP. Computer simulations are performed to investigate the correlation between folding time and...

The quantitative analysis of metallochaperone proteins in biofluids (e.g. blood, liquor) may be a major prerequisite for clinical investigations concerning the structure-function relationships of biologically-active metal cofactor-containing chaperones in protein-misfolding diseases (e.g. Alzheimer's or related diseases). For these purposes, a new state-of-the-art gel electrophoresis [quantitat...

Conformational changes in the prion protein (PrP) seem to be responsible for prion diseases. We have used conformation-dependent chemical-shift measurements and rotational-resonance distance measurements to analyze the conformation of solid-state peptides lacking long-range order, corresponding to a region of PrP designated H1. This region is predicted to undergo a transformation of secondary s...

Amyloid fibril formation is implicated in different human diseases. The transition between native α-helices and nonnative intermolecular β-sheets has been suggested to be a trigger of fibrillation in different conformational diseases. The FF domain of the URN1 splicing factor (URN1-FF) is a small all-α protein that populates a molten globule (MG) at low pH. Despite the fact that this conformati...

Transthyretin (TTR) amyloid fibril formation is observed systemically in familial amyloid polyneuropathy and senile systemic amyloidosis and appears to be the causative agent in these diseases. Herein, we demonstrate conclusively that thyroxine (10.8 microM) inhibits TTR fibril formation efficiently in vitro and does so by stabilizing the tetramer against dissociation and the subsequent conform...