Amyloid deposition is a hallmark of many diseases, such as the Alzheimer's disease. Numerous amyloidogenic proteins, including the islet amyloid polypeptide (IAPP) associated with type II diabetes, are natively unfolded and need to undergo conformational rearrangements allowing the formation of locally ordered structure(s) to initiate self-assembly. Recent studies have indicated that the format...

The study of protein aggregation saw a renaissance in the last decade, when it was discovered that aggregation is the cause of several human diseases, making this field of research one of the most exciting frontiers in science today. Building on knowledge about protein folding energy landscapes, determined using an array of biophysical methods, theory and simulation, new light is now being shed...

Solubilization and reconstitution is one of the key steps in the purification of fibrous proteins and in the clarification of certain of their physical properties. Since the description of amyloid as a fibrous protein (1-3), several preliminary studies in this direction have been reported for the amyloid fibril. Newcombe and Cohen (4) studied the effect of pH changes on solubility of amyloid an...

Aggregation of the amyloid-beta (Abeta) peptide into amyloid plaques is a characteristic feature of Alzheimer's disease neuropathogenesis. We and others have previously demonstrated delayed Abeta aggregation as a consequence of oxidizing a single methionine residue at position 35 (Met-35). Here, we examined the consequences of Met-35 oxidation on the extremely aggregation-prone peptides Abeta1-...

The SH3 domain of the c-Src tyrosine kinase (c-Src-SH3) aggregates to form intertwined dimers and amyloid fibrils at mild acid pHs. In this work, we show that a single mutation of residue Gln128 of this SH3 domain has a significant effect on: (i) its thermal stability; and (ii) its propensity to form amyloid fibrils. The Gln128Glu mutant forms amyloid fibrils at neutral pH but not at mild acid ...

The formation of fibrillar aggregates seems to be a common characteristic of polypeptide chains, although the observation of these aggregates may depend on appropriate experimental conditions. Partially folded intermediates seem to have an important role in the generation of protein aggregates, and a mechanism for this fibril formation considers that these intermediates also correspond to metas...

Oligomeric assemblies of the amyloid -protein (A ) have been implicated in the pathogenesis of Alzheimer’s disease as a primary source of neurotoxicity. Recent in vitro studies have suggested that a 10-residue segment, Ala-21–Ala-30, forms a turn-like structure that nucleates the folding of the full-length A . To gain a mechanistic insight, we simulated A (21–30) folding by using a discrete mol...