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

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Science  13 Mar 2020:
Vol. 367, Issue 6483, pp. 1230-1234
DOI: 10.1126/science.aba3526

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How amyloid can be a substrate of memory

Formation of memories requires changes in the molecular composition of the synapse. How these changes occur and what maintains this altered synaptic composition so that memory can persist are unknown. Hervas et al. report the structure of a synaptic translation regulator called Orb2 isolated from the brains of adult fruit flies that is important for the maintenance and recall of memory. Orb2 forms an amyloid and changes its activity from a translation repressor to an activator. The amyloid core is composed of polar hydrophilic residues, as opposed to the hydrophobic ones found in nonfunctional or pathological amyloids. The structure provides insights into how amyloids could be a stable yet malleable substrate of memory.

Science, this issue p. 1230


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.

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