TY - JOUR
T1 - Cryo-EM structure of a neuronal functional amyloid implicated in memory persistence in Drosophila
AU - Hervas, Ruben
AU - Rau, Michael J.
AU - Park, Younshim
AU - Zhang, Wenjuan
AU - Murzin, Alexey G.
AU - Fitzpatrick, James A.J.
AU - Scheres, Sjors H.W.
AU - Si, Kausik
N1 - Publisher Copyright:
© 2020 American Association for the Advancement of Science. All rights reserved.
PY - 2020/3/13
Y1 - 2020/3/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85081885950&partnerID=8YFLogxK
U2 - 10.1126/science.aba3526
DO - 10.1126/science.aba3526
M3 - Article
C2 - 32165583
AN - SCOPUS:85081885950
SN - 0036-8075
VL - 367
SP - 1230
EP - 1234
JO - Science
JF - Science
IS - 6483
ER -