Review of the chemistry of αS2-casein and the generation of a homologous molecular model to explain its properties

Abstract

alpha(S2)-Casein (alpha(S2)-CN) comprises up to 10% of the casein fraction in bovine milk. The role of alpha(S2)-CN in casein micelles has not been studied in detail in part because of a lack of structural information on the molecule. Interest in the utilization of this molecule in dairy products and nutrition has been renewed by work in 3 areas: biological activity via potentially biologically active peptides, functionality in cheeses and products, and nutrition in terms of calcium uptake. To help clarify the behavior of alpha(S2)-CN in its structure-function relationships in milk and its possible applications in dairy products, this paper reviews the chemistry of the protein and presents a working 3-dimensional molecular model for this casein. The model was produced by threading the backbone sequence of the protein onto a homologous protein: chloride intracellular channel protein-4. Overall, the model is in good agreement with experimental data for the protein, although the amount of helix may be over-predicted. The model, however, offers a unique view of the highly positive C-terminal portion of the molecule as a surface-accessible area. This region may be the site for interactions with kappa-carrageenan, phosphate, and other anions. In addition, most of the physiologically active peptides isolated from alpha(S2)-CN occur in this region. This structure should be viewed as a working model that can be changed as more precise experimental data are obtained.

Plasmin Activity in UHT Milk: Relationship between Proteolysis, Age Gelation, and Bitterness

“…After 1 day of storage, peptides originating from the N-and C-terminal region of α S2 -CN were present ( Figure 2). The C-terminal region of α S2 -CN has previously been shown to be exposed and easily accessible for hydrolysis, 34 Figure 4B), which may be inaccessible for enzymatic hydrolysis. 35 Cleavage of this bond can be additionally hindered by Pro 93 which induces a change in the secondary structure of α S2 -CN.…”

Simultaneous Presence of PrtH and PrtH2 Proteinases in Lactobacillus helveticus Strains Improves Breakdown of the Pure α s1 -Casein

“…Interpretation of hydrolyzed regions by casein 3D modeling. 3D molecular-modeling representations of the caseins, deduced from the data of Kumosinski et al (28) for ␣ s1 -casein, Farrell et al (9) for ␣ s2 -casein, and Kumosinski et al (29) for ␤-casein, are shown in Fig. 4.…”

The dissociated form of κ-casein is the precursor to its amyloid fibril formation

“…All of the caseins belong to the group of 'intrinsically disordered' or 'natively unfolded' proteins as they possess relatively little ordered structure under physiological conditions [12,13]. As a consequence, no casein proteins have been crystallized; however, three-dimensional energy-minimized models are available [14][15][16][17]. With regard to κ-CN, spectroscopic and molecular modelling studies indicate that the monomeric form of the protein adopts a 'horse and rider' conformation with persistent secondary-structural elements/motifs, the most significant being two sets of antiparallel β-sheets which are rich in hydrophobic side chains [15].…”