Cryo-EM structure of a neuronal functional amyloid implicated in memory persistence in <i>Drosophila</i>
Rubén Hervás, Michael Rau, Younshim Park, Wenjuan Zhang, Alexey G. Murzin, James A. J. Fitzpatrick, Sjors H. W. Scheres, Kausik Si
Abstract
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.