A structural dynamics model for how CPEB3 binding to SUMO2 can regulate translational control in dendritic spines

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dc.citation.articleNumbere1010657
dc.citation.issueNumber11
dc.citation.journalTitlePLOS Computational Biology
dc.citation.volumeNumber18
dc.contributor.authorGu, Xinyu
dc.contributor.authorSchafer, Nicholas P.
dc.contributor.authorBueno, Carlos
dc.contributor.authorLu, Wei
dc.contributor.authorWolynes, Peter G.
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2022-12-13T19:11:22Z
dc.date.available2022-12-13T19:11:22Z
dc.date.issued2022
dc.description.abstractA 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.
dc.identifier.citationGu, Xinyu, Schafer, Nicholas P., Bueno, Carlos, et al.. "A structural dynamics model for how CPEB3 binding to SUMO2 can regulate translational control in dendritic spines." <i>PLOS Computational Biology,</i> 18, no. 11 (2022) Public Library of Science: https://doi.org/10.1371/journal.pcbi.1010657.
dc.identifier.digitaljournal-pcbi-1010657
dc.identifier.doihttps://doi.org/10.1371/journal.pcbi.1010657
dc.identifier.urihttps://hdl.handle.net/1911/114106
dc.language.isoeng
dc.publisherPublic Library of Science
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleA structural dynamics model for how CPEB3 binding to SUMO2 can regulate translational control in dendritic spines
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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