Alpha-casein as a molecular chaperone

The caseins are a heterogeneous group of dairy proteins constituting 80% of the protein content of bovine milk. The operational definition of casein is that proportion of total milk protein which precipitates on acidification of milk to a pH value of 4.6 [1]. The remaining dairy proteins, known collectively as whey proteins, do not precipitate. Caseins are synthesised in the mammary gland and are found nowhere else among the plant and animal kingdoms [2]. The casein family of proteins comprises , and -caseins, all with little sequence homology [3]. As their primary function is nutritional, binding large amounts of calcium, zinc and other biologically important metals, amino acid substitutions or deletions have little impact on function. The caseins also lack well-defined structure and as a result their amino acid sequence is less critical to function than in many ‘classic’ globular proteins. As a result, the caseins are one of the most evolutionarily divergent protein families characterised in mammals [2]. Alpha-casein, also known as αS-casein, is in fact two distinct gene products, S1and S2-casein, with the ‘S’ denoting a sensitivity to calcium. Of all the caseins, S1and -casein are predominant in bovine milk, representing 37 and 35% of whole casein respectively, whereas αS2and κ-casein make up 10 and 12% of whole casein, respectively [2].