Amyloid fibrils are filamentous aggregates, with typical diameters of 10 nm and lengths on the order of microns, formed by a large class of peptides and proteins with disparate sequences and with molecular masses ranging from less than 1 kDa to tens of kilodaltons. Figure 1 shows typical amyloid fibrils as they appear in electron microscopy (EM)1 measurements. Current interest in amyloid fibril...

Studies of lysozyme have played a major role over several decades in defining the general principles underlying protein structure, folding, and stability. Following the discovery some 10 years ago that two mutational variants of lysozyme are associated with systemic amyloidosis, these studies have been extended to investigate the mechanism of amyloid fibril formation. This Account describes our...

Amyloid fibrils form in supersaturated solutions via a nucleation and growth mechanism. Although the structural features of amyloid fibrils have become increasingly clearer, knowledge on the thermodynamics of fibrillation is limited. Furthermore, protein aggregation is not a target of calorimetry, one of the most powerful approaches used to study proteins. Here, with β2-microglobulin, a protein...

PC12 cell injury was induced using 20 μM amyloid β-protein 25-35 to establish a model of Alzheimer's disease. The cells were then treated with 5, 10, and 25 μM Schisandrin B. Methylthiazolyldiphenyl-tetrazolium bromide assays and Hoechst 33342 staining results showed that with increasing Schisandrin B concentration, the survival rate of PC12 cells injured by amyloid β-protein 25-35 gradually in...

Amyloidosis consists of approximately 30 protein-folding disorders in which a specific soluble precursor protein aggregates to form the insoluble fibrils amyloid. Insulin is hypothesized localized cutaneous insulin-derived (AIns) amyloidosis. Amyloid deposition at insulin injection sites can interfere with absorption, leading poor glucose control. Despite increasing prevalence diabetes mellitus...

Here we discuss studies of the structure, folding, oligomerization and amyloid fibril formation of several proline mutants of human stefin B, which is a protein inhibitor of lysosomal cysteine cathepsins and a member of the cystatin family. The structurally important prolines in stefin B are responsible for the slow folding phases and facilitate domain swapping (Pro 74) and loop swapping (Pro 7...

Internet Electron. J. Mol. Des. 2003, 1, 000-000 Abstract The determination of the folding mechanisms of proteins is critical to understand the topological change that can propagate Alzheimer's and prion diseases. The associated folding time scale generally precludes the use of molecular dynamics simulations. Here we present the details of the activation-relaxation simulations using the generic...

Prion replication occurs via a template-assisted mechanism, which postulates that the folding pattern of a newly recruited polypeptide chain accurately reproduces that of a template. The concept of prion-like template-assisted propagation of an abnormal protein conformation has been expanded to amyloidogenic proteins associated with Alzheimer, Parkinson, Huntington diseases, amyotrophic lateral...