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Coaggregation of κ‐Casein and β‐Lactoglobulin Produces Morphologically Distinct Amyloid Fibrils
Author(s) -
Raynes Jared K.,
Day Li,
Crepin Pauline,
Horrocks Mathew H.,
Carver John A.
Publication year - 2017
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201603591
Subject(s) - fibril , amyloid (mycology) , chemistry , amyloid fibril , biophysics , peptide , protein aggregation , protein folding , gene isoform , casein , sequence (biology) , protein structure , crystallography , peptide sequence , disulfide bond , biochemistry , biology , amyloid β , medicine , inorganic chemistry , disease , pathology , gene
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.