The dissociated form of κ-casein is the precursor to its amyloid fibril formation

Heath Ecroyd*, David C. Thorn, Yanqin Liu, John A. Carver

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

Abstract

Bovine milk κ-casein forms a self-associating oligomeric micellelike 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 κ-casein form highly structured β-sheet amyloid fibrils. We investigated whether the precursor to κ-casein fibril formation is a dissociated state of the protein or its oligomeric micelle-like form. We show that reduced κ-casein is capable of forming fibrils well below its critical micelle concentration, i.e. at concentrations where only dissociated forms of the protein are present. Moreover, by regulating the degree of disulfide linkages, we were able to investigate how oligomerization of κ-casein influences its propensity for fibril formation under conditions of physiological pH and temperature. Thus, using fractions containing different proportions of multimeric species, we demonstrate that the propensity of the disulfide-linked multimers to form fibrils is inversely related to their size, with monomeric κ-casein being the most aggregation prone.We conclude that dissociated forms of κ-casein are the amyloidogenic precursors to fibril formation rather than oligomeric micelle-like species. The results highlight the role of oligomerization and natural binding partners in preventing amyloid fibril formation by disease-related proteins in vivo.

Original languageEnglish
Pages (from-to)251-260
Number of pages10
JournalBiochemical Journal
Volume429
Issue number2
DOIs
Publication statusPublished - 15 Jul 2010
Externally publishedYes

Fingerprint

Dive into the research topics of 'The dissociated form of κ-casein is the precursor to its amyloid fibril formation'. Together they form a unique fingerprint.

Cite this