Amyloid fibril formation by bovine milk kappa-casein and its inhibition by the molecular chaperones alpha(s-) and beta-casein

D C Thorn, S Meehan, M Sunde, A Rekas, S L Gras, C E MacPhee, C M Dobson, M R Wilson, J A Carver, Cait MacPhee

Research output: Contribution to journalArticlepeer-review

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 kappa-casein. Transmission electron microscopy (TEM) and X-ray fiber diffraction data demonstrated that kappa-casein readily forms amyloid fibrils at 37 degrees C particularly following reduction of its disulfide bonds. The time-dependent increase in thioflavin T fluorescence observed for reduced and nonreduced K-casein at 37 degrees C was suppressed by stoichiometric amounts of alpha(S)- and beta-casein and by the hydrophobic dye 8-anilino-1-naphthalene sulfonate; the inhibition of K-casein fibril formation under these conditions was verified by TEM. Our findings suggest that alpha(S)- and beta-casein are potent inhibitors of K-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.

Original languageEnglish
Pages (from-to)17027-17036
Number of pages10
JournalBiochemistry
Volume44
Issue number51
DOIs
Publication statusPublished - 27 Dec 2005

Keywords

  • HEAT-SHOCK PROTEINS
  • ALPHA-B-CRYSTALLIN
  • APOLIPOPROTEIN C-II
  • CORPORA-AMYLACEA
  • MAMMARY-GLAND
  • EXTRACELLULAR CHAPERONE
  • DISULFIDE BRIDGES
  • CLUSTERIN
  • MECHANISM
  • KINETICS

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