Amyloid Fibril Formation by Bovine Milk κ-Casein and Its Inhibition by the Molecular Chaperones α S - and β-Casein
2005; American Chemical Society; Volume: 44; Issue: 51 Linguagem: Inglês
10.1021/bi051352r
ISSN1943-295X
AutoresDavid C. Thorn, Sarah Meehan, Margaret Sunde, Agata Rekas, Sally L. Gras, Cait E. MacPhee, Christopher M. Dobson, Mark R. Wilson, John A. Carver,
Tópico(s)Prion Diseases and Protein Misfolding
ResumoCaseins 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.
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