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

Ruben Hervas, Michael J. Rau, Younshim Park, Wenjuan Zhang, Alexey G. Murzin, James A.J. Fitzpatrick, Sjors H.W. Scheres, Kausik Si

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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-b 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 ofmemory.

Original languageEnglish
Pages (from-to)1230-1234
Number of pages5
JournalScience
Volume367
Issue number6483
DOIs
StatePublished - Mar 13 2020

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