Structure of Biomimetic Casein Micelles: Critical Tests of the Hydrophobic Colloid and Multivalent-Binding Models Using Recombinant Deuterated and Phosphorylated Β-Casein

47 Pages Posted: 24 Oct 2023

See all articles by Jared Kenneth Raynes

Jared Kenneth Raynes

CSIRO Agriculture and Food

Jitendra Mata

Government of the Commonwealth of Australia - Australian Nuclear Science and Technology Organisation

Karyn L. Wilde

Government of the Commonwealth of Australia - Australian Nuclear Science and Technology Organisation

Sharon M. Kelly

University of Glasgow

Carl Holt

University of Glasgow

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Abstract

Milk contains high concentrations of amyloidogenic casein proteins and is supersaturated with respect to crystalline calcium phosphates such as apatite. Nevertheless, the mammary gland normally remains unmineralized and free of amyloid. Unlike κ-casein, β- and αS-caseins are highly effective mineral chaperones that prevent ectopic and pathological calcification of the mammary gland. Milk invariably contains a mixture of two to five different caseins that act on each other as molecular chaperones. Instead of forming amyloid fibrils, several thousand caseins and hundreds of nanoclusters of amorphous calcium phosphate combine to form fuzzy complexes called casein micelles. To understand the biological functions of the casein micelle its structure needs to be understood better than at present. The location in micelles of the highly amyloidogenic k-casein is disputed. In traditional hydrophobic colloid models, it, alone, forms a stabilizing surface coat that also determines the average size of the micelles. In the recent multivalent-binding model, κ-casein is present throughout the micelle, in intimate contact with the other caseins. To discriminate between these models, a range of biomimetic micelles was prepared using a fixed concentration of the mineral chaperone b-casein and nanoclusters of calcium phosphate, with variable concentrations of κ-casein. A biomimetic micelle was also prepared using a highly deuterated and in vivo phosphorylated recombinant β-casein with calcium phosphate and unlabelled κ-casein. Neutron and X-ray scattering experiments revealed that κ-casein is distributed throughout the micelle, in quantitative agreement with the multivalent-binding model but contrary to the hydrophobic colloid models.

Keywords: Casein micelle, mineral chaperone, calcium phosphate, small-angle scattering, intrinsically disordered protein

Suggested Citation

Raynes, Jared Kenneth and Mata, Jitendra and Wilde, Karyn L. and Kelly, Sharon M. and Holt, Carl, Structure of Biomimetic Casein Micelles: Critical Tests of the Hydrophobic Colloid and Multivalent-Binding Models Using Recombinant Deuterated and Phosphorylated Β-Casein. Available at SSRN: https://ssrn.com/abstract=4608131 or http://dx.doi.org/10.2139/ssrn.4608131

Jared Kenneth Raynes (Contact Author)

CSIRO Agriculture and Food ( email )

Jitendra Mata

Government of the Commonwealth of Australia - Australian Nuclear Science and Technology Organisation ( email )

Locked Bag 2001
Kirrawee DC
Sydney, NSW 2232
Australia

Karyn L. Wilde

Government of the Commonwealth of Australia - Australian Nuclear Science and Technology Organisation ( email )

Locked Bag 2001
Kirrawee DC
Sydney, NSW 2232
Australia

Sharon M. Kelly

University of Glasgow ( email )

Adam Smith Business School
Glasgow, G12 8LE
United Kingdom

Carl Holt

University of Glasgow ( email )

Adam Smith Business School
Glasgow, G12 8LE
United Kingdom

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