BACKGROUND: Amyloids are highly ordered polypeptide aggregates stabilized by a beta-sheet structural core . Though classically associated to pathology, reports on novel functional roles of these proteins have increasingly emerged in the past decade . Moreover, the recent discovery that amyloids formed with rationally designed small peptides can exhibit catalytic reactivity has opened up new opportunities in both biology and biotechnology . The observed activities typically require the binding of divalent metals, giving rise to active metal-amyloid complexes .
METHODS: Peptide (SDIDVFI) was aggregated in vitro . The structure of the self-assembled species was analyzed using fluorescence, transmission electron microscopy, circular dichroism and computational modeling . A kinetic characterization of the emerging catalytic activity was performed .
RESULTS: The peptide self-assembled into canonical amyloids that exhibited catalytic activity towards hydrolysis of the phosphoanhydride bonds of adenosine triphosphate (ATP), partially mimicking an ATPase-like enzyme . Both amyloid formation and activity are shown to depend on manganese (Mn2+) binding . The activity was not restricted to ATP but also affected all other ribonucleotides (GTP, CTP and UTP). Peptides carrying a single aspartate exhibited a similar activity .
CONCLUSIONS: The phosphoanhydride bonds appear as the main specificity target of the Mn2+-amyloid complex . A single aspartate per peptide is sufficient to enable the hydrolytic activity . GENERAL SIGNIFICANCE: Catalytic amyloids are shown for the first time to catalyze the hydrolysis of all four ribonucleotides . Our results should contribute towards understanding the biological implications of amyloid-mediated reactivity as well as in the design of future catalytic amyloids for biotechnological applications.