Coaggregation of κ‐Casein and β‐Lactoglobulin Produces Morphologically Distinct Amyloid Fibrils

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2017-04, Vol.13 (14), p.np-n/a
• Main Authors: Raynes, Jared K., Day, Li, Crepin, Pauline, Horrocks, Mathew H., Carver, John A.
• Format: Article
• Language: English
• Subjects: Agglomeration; Aggregates; Amyloid - chemistry; amyloid fibril; Bonding; casein; Caseins - chemistry; coaggregation; Heating; Lactoglobulins - chemistry; Milk; molecular chaperone; protein aggregation; Protein Aggregation, Pathological; Proteins; Running; Similarity; β‐lactoglobulin
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201603591

The unfolding, misfolding, and aggregation of proteins lead to a variety of structural species. One form is the amyloid fibril, a highly aligned, stable, nanofibrillar structure composed of β‐sheets running perpendicular to the fibril axis. β‐Lactoglobulin (β‐Lg) and κ‐casein (κ‐CN) are two milk proteins that not only individually form amyloid fibrillar aggregates, but can also coaggregate under environmental stress conditions such as elevated temperature. The aggregation between β‐Lg and κ‐CN is proposed to proceed via disulfide bond formation leading to amorphous aggregates, although the exact mechanism is not known. Herein, using a range of biophysical techniques, it is shown that β‐Lg and κ‐CN coaggregate to form morphologically distinct co‐amyloid fibrillar structures, a phenomenon previously limited to protein isoforms from different species or different peptide sequences from an individual protein. A new mechanism of aggregation is proposed whereby β‐Lg and κ‐CN not only form disulfide‐linked aggregates, but also amyloid fibrillar coaggregates. The coaggregation of two structurally unrelated proteins into cofibrils suggests that the mechanism can be a generic feature of protein aggregation as long as the prerequisites for sequence similarity are met. Upon heating together, the milk proteins κ‐casein and β‐lactoglobulin coaggregate to form amyloid fibrils. Cofibrillation of proteins is a rarely observed phenomenon and suggests a generic protein aggregation mechanism as long as sequence similarity requirements are met for both proteins. The results have implications for the ultra‐heat treatment of milk.