RT Journal Article
SR Electronic
T1 Structure of a reversible amyloid fibril formed by the CPEB3 prion-like domain reveals a core sequence involved in translational regulation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.12.07.519389
DO 10.1101/2022.12.07.519389
A1 Flores, Maria D.
A1 Sawaya, Michael R.
A1 Boyer, David R.
A1 Zink, Samantha
A1 Tovmasyan, Susanna
A1 Saucedo, Adrian
A1 Zee, Chih-Te
A1 Cardenas, Jorge
A1 Fioriti, Luana
A1 Rodriguez, Jose A.
YR 2022
UL http://biorxiv.org/content/early/2022/12/07/2022.12.07.519389.abstract
AB The cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a prion-like RNA-binding polypeptide. As a functional prion, CPEB3 is thought to modulate protein synthesis at synapses and enable consolidation of long-term memory in neurons. Here, we report that the prion-like domain 1 of CPEB3 self-assembles into labile amyloid fibrils in vitro. A cryoEM structure of these fibrils reveals an ordered 48-residue core, spanning L103 to F151. CPEB3 constructs lacking this amyloidogenic segment form abnormal puncta in cells when compared to wild type CPEB3, with reduced localization in dormant p-bodies and increased localization in stress granules. Removal of the amyloid core segment in CPEB3 also abolishes its ability to regulate protein synthesis in neurons. Collectively, this evidence suggests that the newly identified amyloidogenic segment within the CPEB3 prion domain is important for its regulated aggregation in cells and suggest its involvement in regulating translational activity and potentially long-term memory formation.Competing Interest StatementJAR is an equity stake holder of MedStruc Inc.