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Science. 2020 Mar 13;367(6483):1230-1234. doi: 10.1126/science.aba3526.

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

Author information

1
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
2
Washington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
4
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
5
Departments of Neuroscience and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
6
Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA.
7
Stowers Institute for Medical Research, Kansas City, MO 64110, USA. ksi@stowers.org.

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-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.

PMID:
32165583
DOI:
10.1126/science.aba3526

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