A biological perspective on the structure and function of caseins and casein micelles

Caseins belong to a larger group of secreted calcium phosphate-binding phosphoproteins that have a natively unfolded conformation. Nearly all members of the group are involved in aspects of calcium phosphate biology and nearly all have recognition sites for phosphorylation by the Golgi protein kinase. In the caseins these are often close together in the primary structure, forming the so-called phosphate centres. Certain highly phosphorylated phosphopeptides derived from the calcium-sensitive caseins will combine with amorphous calcium phosphate to form defined chemical complexes called calcium phosphate nanoclusters. Both the substructure of casein micelles and the partition of salts in milk can be explained quantitatively by the ability of the calcium-sensitive caseins to sequester calcium phosphate and form nanocluster-like structures. A simple stability rule for milk can be derived by applying equilibrium thermodynamics to the process of calcium phosphate sequestration. In principle, the stability rule can be extended to problems of instability encountered in milk-processing operations and to the formulation of other types of high calcium foods.