Cryo-EM structure of a neuronal functional amyloid implicated in memory persistence in Drosophila

How long-lived memories withstand molecular turnover is a fundamental question. Aggregates of a prion-like RNA-binding protein, cytoplasmic polyadenylation element–binding (CPEB) protein, is a putative substrate of long-lasting memories. We isolated aggregated Drosophila CPEB, Orb2, from adult heads and determined its activity and atomic structure, at 2.6-angstrom resolution, using cryo–electron microscopy. Orb2 formed ~75-nanometer-long threefold-symmetric amyloid filaments. Filament formation transformed Orb2 from a translation repressor to an activator and "seed" for further translationally active aggregation. The 31–amino acid protofilament core adopted a cross-β unit with a single hydrophilic hairpin stabilized through interdigitated glutamine packing. Unlike the hydrophobic core of pathogenic amyloids, the hydrophilic core of Orb2 filaments suggests how some neuronal amyloids could be a stable yet regulatable substrate of memory.

Source: ScienceNOW - March 11, 2020 Category: Science Authors: Hervas, R., Rau, M. J., Park, Y., Zhang, W., Murzin, A. G., Fitzpatrick, J. A. J., Scheres, S. H. W., Si, K. Tags: Biochemistry, Neuroscience reports Source Type: news