Casein structures in the context of unfolded proteins

Abstract

Caseins were among the first proteins to be recognised as functional but unfolded. Many others are now known, providing better models of casein behaviour than either detergents or folded proteins. Caseins are members of a paralogous group of unfolded phosphoproteins, some of which share the ability to sequester amorphous calcium phosphate through phosphate centres. Non-covalent interactions of caseins can be through Pro-and Gln-rich sequences. Similar sequences in other unfolded proteins can also form open and highly hydrated structures such as gels, mucus and slimes. Many unfolded proteins, including κ-and αS2-caseins, can form amyloid fibrils under physiological conditions. The sequence-specific interactions that lead to fibrils can be reduced or eliminated by low specificity interactions among a mixture of caseins to yield, instead, amorphous aggregates. The size of amorphous whole casein aggregates is limited by the C-terminal half of κ-casein whose sequence resembles that of a soluble mucin. Disciplines Medicine and Health Sciences | Social and Behavioral Sciences

The functional roles of the unstructured N- and C-terminal regions in αB-crystallin and other mammalian small heat-shock proteins

“…potentially amyloid fibrilforming α-synuclein, to return to its natively unfolded (intrinsically disordered) state (Cox et al 2014;Treweek et al 2015). From our other studies, it is apparent that the unrelated molecular chaperones, clusterin, caseins and 14-3-3ζ, all exhibit a very similar mechanism of ATP-independent sHsp-like chaperone action (Carver et al 2003;Holt et al 2013;Thorn et al 2015;Williams et al 2011). In E. coli, curli proteins (e.g.…”

“…One explanation for sHsp oligomerisation is that it may protect against fibril formation, for example, within the ACD, in addition to the protection provided by the unstructured flanking regions. Other protein oligomers associate for such a reason, as we have shown for the unstructured milk casein proteins in which micelle (oligomer) formation by the four unrelated caseins (either with themselves individually, or with other caseins, or all of them to form the casein micelle in milk) prevents amyloid fibril formation by κ-and α s2 -casein via mutual chaperone interaction and also (principally within the casein micelle) by the chaperone action of the β-and α s1 -caseins (Holt et al 2013;Holt and Carver 2012;Thorn et al 2015). Similarly, transthyretin fibril formation requires initial dissociation from a tetrameric species prior to a conformational change within the monomer which leads to an aggregation-prone intermediate (Colon and Kelly 1992).…”

Structural differences between bovine A1 and A2 β-casein alter micelle self-assembly and influence molecular chaperone activity

“…These results support the SAXS results ( Figure 3) showing the increased number of flexible protein monomers above the CMC for A 2 β-CN. As hydrogen bonding and hydrophobic interactions are proposed to participate in micelle formation (Holt et al, 2013;Thorn et al, 2014), the lower hydrophobicity of A 2 β-CN compared with A 1 β-CN would contribute to this altered equilibrium. Hydrophobic interactions are also thought to be important for the chaperone action of β-CN; however, from the ANS binding results, we would expect A 1 β-CN to have enhanced chaperone activity due to its increased hydrophobicity.…”

Size Separation Techniques for the Characterisation of Cross-Linked Casein: A Review of Methods and Their Applications

“…A schematic illustration of the casein micelle structure, as suggested by Dalgleish [3], is shown in Figure 1. In spite of decades of research, structure of casein micelles and type of interactions between caseins are still a topic of controversial discussion (e.g., [9][10][11] vs. [12,13]. Furthermore, the term casein "micelle" is a rather historical one and gives rise to debates about its appropriateness to describe the structure of these aggregates (e.g., [5,14,15] vs. [16]).…”