Amyloid Fibril Formation by Bovine Milk κ-Casein and Its Inhibition by the Molecular Chaperones αS- and β-Casein

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Abstract
Caseins are a unique and diverse group of proteins present in bovine milk. While their function is presumed to be primarily nutritional, caseins have a remarkable ability to stabilize proteins, i.e., to inhibit protein aggregation and precipitation, that is comparable to molecular chaperones of the small heat-shock protein (sHsp) family. Additionally, sHsps have been shown to inhibit the formation of amyloid fibrils. This study investigated (i) the fibril-forming propensities of casein proteins and their mixture, sodium caseinate, and (ii) the ability of caseins to prevent in vitro fibril formation by κ-casein. Transmission electron microscopy (TEM) and X-ray fiber diffraction data demonstrated that κ-casein readily forms amyloid fibrils at 37 °C particularly following reduction of its disulfide bonds. The time-dependent increase in thioflavin T fluorescence observed for reduced and nonreduced κ-casein at 37 °C was suppressed by stoichiometric amounts of αS- and β-casein and by the hydrophobic dye 8-anilino-1-naphthalene sulfonate; the inhibition of κ-casein fibril formation under these conditions was verified by TEM. Our findings suggest that αS- and β-casein are potent inhibitors of κ-casein fibril formation and may prevent large-scale fibril formation in vivo. Casein proteins may therefore play a preventative role in the development of corpora amylacea, a disorder associated with the accumulation of amyloid deposits in mammary tissue.