Cryo-EM structure of a neuronal functional amyloid implicated in memory persistence in Drosophila
Cryo-EM structure of a neuronal functional amyloid implicated in memory persistence in Drosophila
复制标题
DOI：
10.1126/science.aba3526
复制
发表时间：
2020-03-13
期刊：
影响因子：
56.9
通讯作者：
Si, Kausik
中科院分区：
文献类型：
--
作者：
Hervas, Ruben;Rau, Michael J.;Si, Kausik
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 similar to 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-beta 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.
