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Full-Text Articles in Social and Behavioral Sciences
Dissociation From The Oligomeric State Is The Rate-Limiting Step In Fibril Formation By Kappa-Casein, Heath Ecroyd, Tomas Koudelka, David Thorn, Danielle Williams, Glyn Devlin, Peter Hoffmann, John Carver
Dissociation From The Oligomeric State Is The Rate-Limiting Step In Fibril Formation By Kappa-Casein, Heath Ecroyd, Tomas Koudelka, David Thorn, Danielle Williams, Glyn Devlin, Peter Hoffmann, John Carver
Heath Ecroyd
Amyloid fibrils are aggregated and precipitated forms of protein in which the protein exists in highly ordered, long, unbranching threadlike formations that are stable and resistant to degradation by proteases. Fibril formation is an ordered process that typically involves the unfolding of a protein to partially folded states that subsequently interact and aggregate through a nucleation-dependent mechanism. Here we report on studies investigating the molecular basis of the inherent propensity of the milk protein, kappa-casein, to form amyloid fibrils. Using reduced and carboxymethylated kappa-casein ( RCM kappa-CN), we show that fibril formation is accompanied by a characteristic increase in thioflavin …
The Dissociated Form Of Kappa-Casein Is The Precursor To Its Amyloid Fibril Formation, Heath Ecroyd, David Thorn, Yanqin Liu, John Carver
The Dissociated Form Of Kappa-Casein Is The Precursor To Its Amyloid Fibril Formation, Heath Ecroyd, David Thorn, Yanqin Liu, John Carver
Heath Ecroyd
Bovine milk kappa-casein forms a self-associating oligomeric micelle-like species, in equilibrium with dissociated forms. In its native form, intra- and inter-molecular disulfide bonds lead to the formation of multimeric species ranging from monomers to decamers. When incubated under conditions of physiological pH and temperature, both reduced and non-reduced kappa-casein form highly structured beta-sheet amyloid fibrils. We investigated whether the precursor to kappa-casein fibril formation is a dissociated state of the protein or its oligomeric micelle-like form. We show that reduced kappa-casein is capable of forming fibrils well below its critical micelle concentration, i.e. at concentrations where only dissociated forms of …
Alphab-Crystallin Inhibits The Cell Toxicity Associated With Amyloid Fibril Formation By Kappa-Casein And The Amyloid-Beta Peptide, Francis C. Dehle, Heath Ecroyd, Ian F. Musgrave, John A. Carver
Alphab-Crystallin Inhibits The Cell Toxicity Associated With Amyloid Fibril Formation By Kappa-Casein And The Amyloid-Beta Peptide, Francis C. Dehle, Heath Ecroyd, Ian F. Musgrave, John A. Carver
Heath Ecroyd
Amyloid fibril formation is associated with diseases such as Alzheimer’s, Parkinson’s, and prion diseases. Inhibition of amyloid fibril formation by molecular chaperone proteins, such as the small heat-shock protein αB-crystallin, may play a protective role in preventing the toxicity associated with this form of protein misfolding. Reduced and carboxymethylated κ-casein (RCMκ-CN), a protein derived from milk, readily and reproducibly forms fibrils at physiological temperature and pH. We investigated the toxicity of fibril formation by RCMκ-CN using neuronal model PC12 cells and determined whether the inhibition of fibril formation altered its cell toxicity. To resolve ambiguities in the literature, we also …