The primary nucleation step in amyloid fibril formation can, depending on the nature of peptide sequence, occur in one step, straight from a dilute solution, or in multiple steps, via oligomers or disordered aggregates. The precise kinetic pathways of these processes are poorly understood. Employing forward flux sampling and a midresolution coarse-grained force field, we analyzed the reactive p...

Myxococcus xanthus fibrils are cell surface-associated structures composed of roughly equal amounts of polysaccharide and protein. The level of M. xanthus polysaccharide production under different conditions in the wild type and in several mutants known to have alterations in fibril production was investigated. Wild-type exopolysaccharide increased significantly as cells entered the stationary ...

We have previously shown that amyotrophic lateral sclerosis with cognitive impairment can be characterized by pathologic inclusions of microtubule-associated protein tau (tau) phosphorylated at Thr(175) (pThr(175)) in association with GSK3β activation. We have now examined whether pThr(175) induces GSK3β activation and whether this leads to pathologic fibril formation through Thr(231) phosphory...

Prion fibrils, which are a hallmark for neurodegenerative diseases, have recently been found to exhibit the structural diversity that governs disease pathology. Despite our recent finding concerning the role of the disease-specific structure of prion fibrils in determining their elastic properties, the mechanical deformation mechanisms and fracture properties of prion fibrils depending on their...

Self-assembly of misfolded proteins into ordered fibrillar aggregates known as amyloid results in numerous human diseases. Despite an increasing number of proteins and peptide fragments being recognised as amyloidogenic, how these amyloid aggregates assemble remains unclear. In particular, the identity of the nucleating species, an ephemeral entity that defines the rate of fibril formation, rem...

Understanding the structural heterogeneity inherent in the process of amyloid fibril formation is an important goal of protein aggregation studies. Structural heterogeneity in amyloid fibrils formed by a protein manifests itself in fibrils varying in internal structure and external appearance, and may originate from molecular level variations in the internal structure of the cross-β motif. Amyl...

PURPOSE The size and organization of stromal collagen fibrils influence the biomechanical and optical properties of the cornea and hence its function. How fibrillar structure varies with position across the cornea has not been fully characterized. The present study was designed to quantify the collagen fibril spacing and diameter across the normal human cornea and to relate this to the properti...

Ure2p is the protein determinant of the Saccharomyces cerevisiae prion state [URE3]. Constitutive overexpression of the HSP70 family member SSA1 cures cells of [URE3]. Here, we show that Ssa1p increases the lag time of Ure2p fibril formation in vitro in the presence or absence of nucleotide. The presence of the HSP40 co-chaperone Ydj1p has an additive effect on the inhibition of Ure2p fibril fo...

BACKGROUND Type I collagen is the most common protein among higher vertebrates. It forms the basis of fibrous connective tissues (tendon, chord, skin, bones) and ensures mechanical stability and strength of these tissues. It is known, however, that separate triple-helical collagen macromolecules are unstable at physiological temperatures. We want to understand the mechanism of collagen stabilit...

the mechanism and the parameters affecting the matrix-fibril morphology in melt spun polyblend fibers are discussed. the properties of polymeric blends depend considerably on their final morphologies. blending of two miscible polymers, normally gives rise to formation of a single-phase morphology while blending of two immiscible polymers can create a two or three (in case of using compatibilize...