Functional and dysfunctional folding, association and aggregation of caseins
Date
2019
Authors
Carver, John
Holt, Carl
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Academic Press
Abstract
Caseins are a group of closely related intrinsically disordered proteins (IDPs), best
known for their occurrence in milk as stable, polydisperse, roughly spherical, amorphous particles, typically containing thousands of protein chains and hundreds of
nanoclusters of calcium phosphate. The particles are called casein micelles though their
structure bears no resemblance to detergent micelles. Caseins have an open and flexible conformation with a preponderance of poly-L-proline II secondary structure and
hence cannot be described as hydrophobic proteins. Individually, and in combination,
they associate through polar and non-polar interactions to form polydisperse fuzzy
complexes (including the native casein micelle) while retaining their hydrated and flexible conformation to a large degree. Like many other IDPs, caseins are prone to form
cytotoxic amyloid fibrils. However, they are also highly effective molecular chaperones
so that a mixture of different caseins can form fuzzy complexes that are often selflimiting in size and, within which, amyloid fibril formation is suppressed. The remarkable
ability of caseins to sequester nanoclusters of calcium phosphate in stable complexes is
due to their flexible conformation and multiply-phosphorylated short sequences. These
features combine to form a dense peptide shell around the calcium phosphate making
the core-shell complex thermodynamically stable, even at high calcium and phosphate
concentrations. Thus, the casein micelle provides a readily digested, high calcium food
for the neonate. It also preserves the functional properties of caseins as IDPs and protects the mammary gland against amyloid formation and pathological calcification,
dysfunctional processes that would reduce the future reproductive success of the
mother
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Advances in Protein Chemistry
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Journal article
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2037-12-31
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