Functional and dysfunctional folding, association and aggregation of caseins.

  title={Functional and dysfunctional folding, association and aggregation of caseins.},
  author={John A. Carver and Carl Holt},
  journal={Advances in protein chemistry and structural biology},
  • J. CarverC. Holt
  • Published 2019
  • Medicine, Chemistry
  • Advances in protein chemistry and structural biology

Structural Biology of Calcium Phosphate Nanoclusters Sequestered by Phosphoproteins

Application of physico-chemical principles and properties of complexes formed by casein, osteopontin, and recombinant phosphopeptides to blood serum, milk, urine, and resting saliva is described to show that under physiological conditions they are in the stable region of their stability diagram and so cannot cause soft tissue calcification.

Are casein micelles extracellular condensates formed by liquid‐liquid phase separation?

Casein micelles are extracellular polydisperse assemblies of unstructured casein proteins. Caseins are the major component of milk. Within casein micelles, casein molecules are stabilised by binding


Multivalent ions and biomolecules: Attempting a comprehensive perspective

The attempt of a comprehensive discussion is guided by the idea that there are not only important differences and specific phenomena with regard to the effects of multivalent ions on the main systems, but also important similarities, to bridge physico‐chemical mechanisms, concepts of soft matter, and biological observations and connect the different communities further.

Amyloidogenicity of peptides targeting diabetes and obesity.

Salt partition, ion equilibria, and the structure, composition, and solubility of micellar calcium phosphate in bovine milk with added calcium salts.

The conclusion is that the added calcium caused an increase in the concentration of the MCP and decreased its solubility without changing its amorphous structure or chemical composition.



Invited review: Caseins and the casein micelle: their biological functions, structures, and behavior in foods.

Competent noncasein phosphoproteins have similar patterns of phosphorylation and the same type of flexible, unfolded conformation as caseins and may be of general physiological importance in preventing calcification of other biofluids and soft tissues.

Molecular Chaperone-like Properties of an Unfolded Protein, αs-Casein*

This paper shows that αs-casein, abundant in mammalian milk, which has no well defined secondary and tertiary structure but exits in nature as a micellar aggregate, can prevent a variety of unrelated proteins/enzymes against thermal-, chemical-, or light-induced aggregation.

Amyloid fibril formation by bovine milk kappa-casein and its inhibition by the molecular chaperones alphaS- and beta-casein.

It is suggested that alphaS- and beta- casein are potent inhibitors of kappa-casein fibril formation and may prevent large-scale fibrils formation in vivo and play a preventative role in the development of corpora amylacea, a disorder associated with the accumulation of amyloid deposits in mammary tissue.

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

It is demonstrated that the propensity of the disulfide-linked multimers to form fibrils is inversely related to their size, with monomeric kappa-casein being the most aggregation prone.

Coaggregation of κ-Casein and β-Lactoglobulin Produces Morphologically Distinct Amyloid Fibrils.

It is shown that β-Lg and κ-CN coaggregate to form morphologically distinct co-amyloid fibrillar structures, a phenomenon previously limited to protein isoforms from different species or different peptide sequences from an individual protein.

Dissociation from the Oligomeric State Is the Rate-limiting Step in Fibril Formation by κ-Casein*

Fibril formation by RCMκ-CN occurs through a novel mechanism whereby the rate-limiting step is the dissociation of an amyloidogenic precursor from an oligomeric state rather than the formation of stable nuclei, as has been described for most other fibril-forming systems.

Environmental Influences on Bovine κ-Casein: Reduction and Conversion to Fibrillar (Amyloid) Structures

On the basis of three-dimensional molecular modeling predictions, there may exist a tyrosine-rich repeated sheet-turnsheet motif in κ-casein, which may allow for the stacking of the molecules into fibrillar structures, and near-ultraviolet CD and thioflavin-T binding studies on RCM-κ- casein support this concept.