Skip navigation
Skip navigation

Methionine Oxidation Enhances κ-Casein Amyloid Fibril Formation

Koudelka, Tomas; Dehle, Francis C.; Musgrave, Ian F.; Hoffmann, Peter; Carver, John

Description

The effects of protein oxidation, for example of methionine residues, are linked to many diseases, including those of protein misfolding, such as Alzheimer's disease. Protein misfolding diseases are characterized by the accumulation of insoluble proteinaceous aggregates comprised mainly of amyloid fibrils. Amyloid-containing bodies known as corpora amylacea (CA) are also found in mammary secretory tissue, where their presence slows milk flow. The major milk protein κ-casein readily forms...[Show more]

dc.contributor.authorKoudelka, Tomas
dc.contributor.authorDehle, Francis C.
dc.contributor.authorMusgrave, Ian F.
dc.contributor.authorHoffmann, Peter
dc.contributor.authorCarver, John
dc.date.accessioned2015-12-10T23:09:12Z
dc.identifier.issn0021-8561
dc.identifier.urihttp://hdl.handle.net/1885/63380
dc.description.abstractThe effects of protein oxidation, for example of methionine residues, are linked to many diseases, including those of protein misfolding, such as Alzheimer's disease. Protein misfolding diseases are characterized by the accumulation of insoluble proteinaceous aggregates comprised mainly of amyloid fibrils. Amyloid-containing bodies known as corpora amylacea (CA) are also found in mammary secretory tissue, where their presence slows milk flow. The major milk protein κ-casein readily forms amyloid fibrils under physiological conditions. Milk exists in an extracellular oxidizing environment. Accordingly, the two methionine residues in κ-casein (Met95 and Met 106) were selectively oxidized and the effects on the fibril-forming propensity, cellular toxicity, chaperone ability, and structure of κ-casein were determined. Oxidation resulted in an increase in the rate of fibril formation and a greater level of cellular toxicity. β-Casein, which inhibits κ-casein fibril formation in vitro, was less effective at suppressing fibril formation of oxidized κ-casein. The ability of κ-casein to prevent the amorphous aggregation of target proteins was slightly enhanced upon methionine oxidation, which may arise from the protein's greater exposed surface hydrophobicity. No significant changes to κ-casein's intrinsically disordered structure occurred upon oxidation. The enhanced rate of fibril formation of oxidized κ-casein, coupled with the reduced chaperone ability of β-casein to prevent this aggregation, may affect casein-casein interaction within the casein micelle and thereby promote κ-casein aggregation and contribute to the formation of CA.
dc.publisherAmerican Chemical Society
dc.sourceJournal of Agricultural and Food Chemistry
dc.subjectKeywords: Alzheimer's disease; Amorphous aggregation; Amyloid fibril; Amyloid fibril formation; Casein micelles; Cellular toxicities; Disordered structures; Extracellular; Fibril formation; In-vitro; methionine; Methionine oxidation; Methionine residues; Milk prote amyloid fibril; casein proteins; methionine; oxidation
dc.titleMethionine Oxidation Enhances κ-Casein Amyloid Fibril Formation
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume60
dc.date.issued2012
local.identifier.absfor030406 - Proteins and Peptides
local.identifier.ariespublicationU4217927xPUB799
local.type.statusPublished Version
local.contributor.affiliationKoudelka, Tomas, University of Adelaide
local.contributor.affiliationDehle, Francis C., University of Adelaide
local.contributor.affiliationMusgrave, Ian F., University of Adelaide
local.contributor.affiliationHoffmann, Peter, The University of Adelaide
local.contributor.affiliationCarver, John, College of Physical and Mathematical Sciences, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue16
local.bibliographicCitation.startpage4144−4155
local.identifier.doi10.1021/jf205168t
local.identifier.absseo970103 - Expanding Knowledge in the Chemical Sciences
dc.date.updated2016-02-24T10:45:53Z
local.identifier.scopusID2-s2.0-84860336481
local.identifier.thomsonID000303139600022
CollectionsANU Research Publications

Download

File Description SizeFormat Image
01_Koudelka_Methionine_Oxidation_Enhances_2012.pdf2.26 MBAdobe PDF    Request a copy


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  19 May 2020/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator