Amyloid aggregation of Bacillus circulans xylanase under a native condition and its modulation by beta‐amyloid‐derived peptide fragments
Timothy Charlton, Vandan Shah, Tonianna Lynch, Jason Candreva, Edward Chau, Yan Xi Yang, Hyunjoo Kim, Amy Wood, Jin Ryoun Kim
Aggregation of intrinsically disordered proteins into fibrils is implicated in many neurodegenerative diseases. Amyloid aggregation is a generic property of proteins as evidenced by globular proteins that often form amyloid aggregates under partially denaturing conditions. Recently, multiple lines of evidence suggest that amyloid aggregation of globular proteins can also occur under native conditions. Unfortunately, the amyloid aggregation under native conditions has been demonstrated with only a handful of cases. Engineering a globular protein’s amyloid aggregation may benefit from its fusion to an amyloid‐derived fragment with reduced aggregation propensity. Unfortunately, the impacts of such fragments on the amyloid aggregation under native conditions have yet to be examined. In this study, we show that a globular protein, Bacillus circulans xylanase (BCX), can aggregate to form amyloid fibrils under a native condition. When mixed with or fused to BCX, the non‐self‐aggregating fragments, KLVFWAK and ELVFWAE – which were derived from beta‐amyloid (Abeta) – modulated the BCX amyloid aggregation to a different extent. This study also provides insight into a correlation between kinetic stability and amyloid aggregation of BCX, and supports a view that the Abeta‐derived fragments can be useful for modulating amyloid aggregation of some, though not all, proteins.
Circular dichroism, Secondary structure, Aggregation, Thermal stability, Protein folding, Chemical stability, Thermodynamics, Biochemistry