期刊
PLOS BIOLOGY
卷 14, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.1002361
关键词
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资金
- SIMR
- Comunidad de Madrid [S2011/BMD-2457]
- Centro de Investigacion Biomedica en Red sobre Enfermedades Respiratorias (CIBERES)
- Core Research for Evolutional Science and Technology (CREST) from the Japan Science and Technology Agency
- (Synapse and Neurocircuit Pathology) from the Ministry of Education, Culture, Sports, Science, and Technology
- Health Labour Sciences Research Grant for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare, Japan
- Fundacion Ferrer (Severo Ochoa fellowship)
- Canon Foundation
- MECD
- MINECO
- Japan Intractable Disease Research Foundation
- [SAF2013-49179-C2-1-R JPND_CD_FP-688-059 (AC14/00037 ISCIII)]
- [SAF2013-49179-C2-2-R JPND_CD_FP-688-059 (AC14/00037 ISCIII)]
- [BFU2012-36825]
- [CTQ2011-22514]
Amyloids are ordered protein aggregates that are typically associated with neurodegenerative diseases and cognitive impairment. By contrast, the amyloid-like state of the neuronal RNA binding protein Orb2 in Drosophila was recently implicated in memory consolidation, but it remains unclear what features of this functional amyloid-like protein give rise to such diametrically opposed behaviour. Here, using an array of biophysical, cell biological and behavioural assays we have characterized the structural features of Orb2 from the monomer to the amyloid state. Surprisingly, we find that Orb2 shares many structural traits with pathological amyloids, including the intermediate toxic oligomeric species, which can be sequestered in vivo in hetero-oligomers by pathological amyloids. However, unlike pathological amyloids, Orb2 rapidly forms amyloids and its toxic intermediates are extremely transient, indicating that kinetic parameters differentiate this functional amyloid from pathological amyloids. We also observed that a well-known anti-amyloidogenic peptide interferes with long-term memory in Drosophila. These results provide structural insights into how the amyloid-like state of the Orb2 protein can stabilize memory and be nontoxic. They also provide insight into how amyloid-based diseases may affect memory processes.
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