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 to calcium phosphate nanoclusters and, by acting as molecular chaperones, through multivalent interactions. In the light of such interactions, we discuss whether casein micelles can be considered as extracellular condensates formed by liquid-liquid phase separation. We analyse the sequence, structure and interactions of caseins in comparison with proteins forming intracellular condensates. Furthermore, we review the similarities between caseins and small heat-shock proteins whose chaperone activity is linked to phase separation of proteins. By bringing these observations together, we describe a regulatory mechanism for protein condensates, as exemplified by casein micelles.
Keywords: biomolecular condensate; casein; casein micelle; liquid-liquid phase separation; molecular chaperone; multivalent interactions; nanocluster; protein aggregation.
© 2022 Federation of European Biochemical Societies.