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Title: A structural dynamics model for how CPEB3 binding to SUMO2 can regulate translational control in dendritic spines
A prion-like RNA-binding protein, CPEB3, can regulate local translation in dendritic spines. CPEB3 monomers repress translation, whereas CPEB3 aggregates activate translation of its target mRNAs. However, the CPEB3 aggregates, as long-lasting prions, may raise the problem of unregulated translational activation. Here, we propose a computational model of the complex structure between CPEB3 RNA-binding domain (CPEB3-RBD) and small ubiquitin-like modifier protein 2 (SUMO2). Free energy calculations suggest that the allosteric effect of CPEB3-RBD/SUMO2 interaction can amplify the RNA-binding affinity of CPEB3. Combining with previous experimental observations on the SUMOylation mode of CPEB3, this model suggests an equilibrium shift of mRNA from binding to deSUMOylated CPEB3 aggregates to binding to SUMOylated CPEB3 monomers in basal synapses. This work shows how a burst of local translation in synapses can be silenced following a stimulation pulse, and explores the CPEB3/SUMO2 interplay underlying the structural change of synapses and the formation of long-term memories.  more » « less
Award ID(s):
2019745 2014141
PAR ID:
10416785
Author(s) / Creator(s):
; ; ; ;
Editor(s):
Chen, Shi-Jie
Date Published:
Journal Name:
PLOS Computational Biology
Volume:
18
Issue:
11
ISSN:
1553-7358
Page Range / eLocation ID:
e1010657
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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