Current concepts of casein and casein micelle structure, interactions, and dynamics

Caseins were shown to be unfolded proteins nearly 70 years ago, but the consequences for casein structure and stability were little appreciated. Instead, casein micelles were modeled as either hydrophobic colloids stabilized by κ-casein, or as expanded but largely rigid proteins with secondary and tertiary structures like globular proteins. All caseins are, however, dynamic and disordered in conformation with a preponderance of poly-l-proline type-II secondary structure. They can act as molecular chaperones and form amyloid fibrils. Their interactions can be strong and specific in forming the cross-β-sheet structure of amyloid fibrils, strong but less specific in binding to nanoclusters of calcium phosphate in the casein micelle, or of lower specificity in forming dynamic multivalent interactions. Thus the casein micelle is built around strong interactions with the calcium phosphate nanoclusters, whereas weaker, multivalent, casein–casein interactions make the casein micelle a highly dynamic structure.