Biological amyloids: A scaffold with chemical reactivity.

Discoveries showing that biological amyloids can catalyze chemical reactions challenge the long-held view that amyloids, functional and pathological, are chemically inert. Although studies remain limited, computational and high-resolution structural work is beginning to uncover key mechanisms. For instance, α-synuclein amyloids were shown to catalyze adenosine triphosphate (ATP) hydrolysis through a structural rearrangement around a lysine-rich substrate-binding cavity. This review summarizes reported chemical reactivities and mechanistic insights for α-synuclein, amyloid-β, and glucagon, the only biological amyloids evaluated so far. To advance this field, future research must assess the biological significance of amyloid catalysis in living cells, expand to additional protein amyloids and structural polymorphs, and explore the full repertoire of substrates and chemical transformations accessible to amyloids.