title: Dephosphorylation of alpha(s)- and beta-caseins and its effect on chaperone activity: a structural and functional investigation.
abstract: Milk casein proteins can act as molecular chaperones: under conditions of stress, such as elevated temperature, molecular chaperones stabilize proteins from unfolding, aggregating, and precipitating. In this study, alpha(s)- and beta-caseins were dephosphorylated using alkaline phosphatase. A structural and functional investigation was undertaken to determine the effect of dephosphorylation on the chaperone activity of alpha(s)- and beta-caseins against two types of protein misfolding, i.e., amorphous aggregation and amyloid fibril assembly. The dephosphorylation of alpha(s)- and beta-caseins resulted in a decrease in the chaperone efficiency against both heat- and reduction-induced amorphously aggregating target proteins. In contrast, dephosphorylation had no effect on the chaperone activity of alpha(s)- and beta-caseins against the amyloid-forming target protein kappa-casein. Circular dichroism and fluorescence spectroscopic data indicated that the loss of negative charge associated with dephosphorylation led to an increase in ordered structure of alpha(s)- and beta-caseins. It is concluded that the flexible, dynamic, and relatively unstructured and amphiphatic nature of alpha(s)- and beta-caseins is important in their chaperone action.
authors.affiliation: School of Chemistry and Physics, The University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: Tomas
authors.initials: T
authors.lastname: Koudelka
authors.forename: Peter
authors.initials: P
authors.lastname: Hoffmann
authors.forename: John A
authors.initials: JA
authors.lastname: Carver
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D002364:Caseins / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D018832:Molecular Chaperones / Q000502:physiology*; D010766:Phosphorylation; D017510:Protein Folding; D013050:Spectrometry, Fluorescence; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D002364:Caseins; D018832:Molecular Chaperones; D000469:Alkaline Phosphatase