On the structural definition of amyloid fibrils and other polypeptide aggregates.
ABSTRACT Amyloid fibrils occur inside the human body, associated with ageing or a group of diseases that includes, amongst others, Alzheimer's disease, atherosclerosis and type II diabetes. Many natural polypeptide chains are able to form amyloid fibrils in vivo or in vitro, and this ability has been suggested to represent an inherent consequence of the chemical structure of the polypeptide chain. Recent literature has provided a wealth of information about the structure of aggregates, precipitates, amyloid fibrils and other types of fibrillar polypeptide assemblies. However, the biophysical meaning associated with these terms can differ considerably depending on the context of their usage. This overview presents a structural comparison of amyloid fibrils and other types of polypeptide assemblies and defines amyloid fibrils, based on structural considerations, as fibrillar polypeptide aggregates with a cross-beta conformation.
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Article: Protein Stability in Shear Flow
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ABSTRACT: Small heat shock proteins (sHsps) are conserved across species and are important in stress tolerance. Many sHsps exhibit chaperone-like activity in preventing aggregation of target proteins, keeping them in a folding–competent state and refolding them by themselves or in concert with other ATP-dependent chaperones. Mutations in human sHsps result in myopathies, neuropathies and cataract. Their expression is modulated in diseases such as Alzheimer’s, Parkinson’s and cancer. Their ability to bind Cu2 +, and suppress generation of reactive oxygen species (ROS) may have implications in Cu2 +-homeostasis and neurodegenerative diseases. Circulating αB-crystallin and Hsp27 in the plasma may exhibit immunomodulatory and anti-inflammatory functions. αB-crystallin and Hsp20 exhitbit anti-platelet aggregation: these beneficial effects indicate their use as potential therapeutic agents. sHsps have roles in differentiation, proteasomal degradation, autophagy and development. sHsps exhibit a robust anti-apoptotic property, involving several stages of mitochondrial-mediated, extrinsic apoptotic as well as pro-survival pathways. Dynamic N- and C-termini and oligomeric assemblies of αB-crystallin and Hsp27 are important factors for their functions. We propose a “dynamic partitioning hypothesis” for the promiscuous interactions and pleotropic functions exhibited by sHsps. Stress tolerance and anti-apoptotic properties of sHsps have both beneficial and deleterious consequences in human health and diseases. Conditional and targeted modulation of their expression and/or activity could be used as strategies in treating several human disorders. The review attempts to provide a critical overview of sHsps and their divergent roles in cellular processes particularly in the context of human health and disease.Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics 12/2014; 1854(4). DOI:10.1016/j.bbapap.2014.12.019 · 3.19 Impact Factor
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ABSTRACT: We investigated the effects of pH (1.6–2.4), NaCl and CaCl2 (0–100 mm) on the kinetics of β-lactoglobulin fibril formation during heating at 80 °C. The morphology of fibrils was also examined. At pH 1.8–2.4 fibril formation occurred slightly faster with decreasing pH. At pH 1.6 fibril formation during the growth phase occurred much faster than at any other pH. Fibril morphology was unchanged between pH 1.6 and pH 2.0. Addition of NaCl or CaCl2 accelerated fibril formation during the growth phase, and CaCl2 shortened the lag phase as well. Worm-like fibrils were seen at ≥60 mm NaCl or ≥33 mm CaCl2, and these had a persistence length which was much shorter than the long semi-flexible fibrils formed without salts. The efficiency of fibril formation can be substantially enhanced by varying pH and salt concentration.International Dairy Journal 09/2010; 20(9):571-579. DOI:10.1016/j.idairyj.2010.02.014 · 2.30 Impact Factor