Caseins as rheomorphic proteins: interpretation of primary and secondary structures of the α_S1-, β- and κ-caseins

Abstract

Caseins are members of a class of proteins with extremely open and flexible conformations. Here, we consider what features of their sequences are important in maintaining such a structure. Primary structures of the αS1-, β- and κ-caseins from species including the cow, sheep, rat, mouse, rabbit and guinea pig were aligned both by a variety of automatic multiple alignment procedures, and manually, to identify conserved features. Fully conserved residues in the mature proteins were unusually rare and involved mainly residues that have high mutation rates in conventional alignment scoring schemes. Autocorrelation of sequences using residue mutation rate scores as measures of similarity revealed that around the PQNI conserved sequence of β-caseins there appear to be repeated sequences similar to Pro-rich domain-linking peptides found in a number of other proteins. Other cryptic repeats were found in αS1-caseins. Predicted secondary structures were calculated and it is argued that apart from the regions around the centres of phosphorylation, the caseins are essentially of the all-β-strand type. However, condensation into β-sheets is inhibited by certain of the conserved features of the primary structure, allowing the proteins to maintain an open and mobile (rheomorphic) conformation.