Coaggregation of κ-Casein and β-Lactoglobulin Produces Morphologically Distinct Amyloid Fibrils.
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.
CSIRO Agriculture and Food, Werribee, Victoria, 3031, Australia.
Jared K
JK
Raynes
AgResearch Limited, Grasslands Research Centre, Tennent Drive, Palmerston North, 4442, New Zealand.
Li
L
Day
École Nationale Supérieure de Chimie, Biologie et Physique, Bordeaux, 33607, France.
Pauline
P
Crepin
Proteostasis and Disease Research Centre, School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, 2522, Australia.
Mathew H
MH
Horrocks
Research School of Chemistry, The Australian National University, Acton, Australian Capital Territory, 2601, Australia.
John A
JA
Carver
D000682:Amyloid / Q000737:chemistry*; D002364:Caseins / Q000737:chemistry*; D007782:Lactoglobulins / Q000737:chemistry*; D066263:Protein Aggregation, Pathological
D000682:Amyloid; D002364:Caseins; D007782:Lactoglobulins
amyloid fibril; casein; coaggregation; molecular chaperone; protein aggregation; β-lactoglobulin