(627d) Amyloid Aggregation of Bacillus Circulans Xylanase Under Native Conditions and Its Modulation By ?-Amyloid-Derived Peptide Fragments

The 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 have suggested that the amyloid aggregation of globular proteins can also occur under native conditions. Unfortunately, amyloid aggregation under native conditions has been demonstrated in only a handful of cases.

In this research, we studied the amyloid aggregation of a globular protein, Bacillus circulans xylanase (BCX)—an endo‐β‐1-4‐xylanase catalyzing the hydrolysis of the polysaccharide xylan—upon fusion or addition of non‐self‐aggregating fragments, KLVFWAK and ELVFWAE, which were derived from the key amyloidogenic domain of β-amyloid (Aβ). To the best of our knowledge, this is the first time that the wild‐type BCX has been shown to form amyloid fibrils under native conditions. Our results also support the view that the kinetic stability of BCX is closely related to its amyloid aggregation. Moreover, our study demonstrates that the impacts of the non‐self‐aggregating Aβ‐derived fragments on BCX amyloid aggregation might vary depending on whether the fragments were fused to or simply mixed with BCX. Collectively, this study 1) provides insight into a globular protein's amyloid aggregation under native conditions, its kinetic stability, and the modulation thereof by Aβ‐derived, non‐self‐aggregating fragments and 2) demonstrates that these fragments are useful for modulating amyloid aggregation for some, though not all, proteins.