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Article: Divergent CPEB prion-like domains reveal different assembly mechanisms for a generic amyloid-like fold

TitleDivergent CPEB prion-like domains reveal different assembly mechanisms for a generic amyloid-like fold
Authors
KeywordsCytoplasmic polyadenylation element binding protein (CPEB)
Functional amyloids
Prion-like protein
Memory persistence
Coiled coil
Issue Date2021
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcbiol/
Citation
BMC Biology, 2021, v. 19, article no. 43 How to Cite?
AbstractBackground: Amyloids are ordered, insoluble protein aggregates, characterized by a cross-β sheet quaternary structure in which molecules in a β-strand conformation are stacked along the filament axis via intermolecular interactions. While amyloids are typically associated with pathological conditions, functional amyloids have also been identified and are present in a wide variety of organisms ranging from bacteria to humans. The cytoplasmic polyadenylation element-binding (CPEB) prion-like protein is an mRNA-binding translation regulator, whose neuronal isoforms undergo activity-dependent aggregation, a process that has emerged as a plausible biochemical substrate for memory maintenance. CPEB aggregation is driven by prion-like domains (PLD) that are divergent in sequence across species, and it remains unknown whether such divergent PLDs follow a similar aggregating assembly pathway. Here, we describe the amyloid-like features of the neuronal Aplysia CPEB (ApCPEB) PLD and compare them to those of the Drosophila ortholog, Orb2 PLD. Results: Using in vitro single-molecule and bulk biophysical methods, we find transient oligomers and mature amyloid-like filaments that suggest similarities in the late stages of the assembly pathway for both ApCPEB and Orb2 PLDs. However, while prior to aggregation the Orb2 PLD monomer remains mainly as a random coil in solution, ApCPEB PLD adopts a diversity of conformations comprising α-helical structures that evolve to coiled-coil species, indicating structural differences at the beginning of their amyloid assembly pathways. Conclusion: Our results indicate that divergent PLDs of CPEB proteins from different species retain the ability to form a generic amyloid-like fold through different assembly mechanisms.
Persistent Identifierhttp://hdl.handle.net/10722/299291
ISSN
2023 Impact Factor: 4.4
2023 SCImago Journal Rankings: 1.787
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHervás, R-
dc.contributor.authordel Carmen Fernández-Ramírez, M-
dc.contributor.authorGalera-Prat, A-
dc.contributor.authorSuzuki, M-
dc.contributor.authorNagai, Y-
dc.contributor.authorBruix, M-
dc.contributor.authorMenéndez, M-
dc.contributor.authorLaurents, DV-
dc.contributor.authorCarrión-Vázquez, M-
dc.date.accessioned2021-05-10T06:59:43Z-
dc.date.available2021-05-10T06:59:43Z-
dc.date.issued2021-
dc.identifier.citationBMC Biology, 2021, v. 19, article no. 43-
dc.identifier.issn1741-7007-
dc.identifier.urihttp://hdl.handle.net/10722/299291-
dc.description.abstractBackground: Amyloids are ordered, insoluble protein aggregates, characterized by a cross-β sheet quaternary structure in which molecules in a β-strand conformation are stacked along the filament axis via intermolecular interactions. While amyloids are typically associated with pathological conditions, functional amyloids have also been identified and are present in a wide variety of organisms ranging from bacteria to humans. The cytoplasmic polyadenylation element-binding (CPEB) prion-like protein is an mRNA-binding translation regulator, whose neuronal isoforms undergo activity-dependent aggregation, a process that has emerged as a plausible biochemical substrate for memory maintenance. CPEB aggregation is driven by prion-like domains (PLD) that are divergent in sequence across species, and it remains unknown whether such divergent PLDs follow a similar aggregating assembly pathway. Here, we describe the amyloid-like features of the neuronal Aplysia CPEB (ApCPEB) PLD and compare them to those of the Drosophila ortholog, Orb2 PLD. Results: Using in vitro single-molecule and bulk biophysical methods, we find transient oligomers and mature amyloid-like filaments that suggest similarities in the late stages of the assembly pathway for both ApCPEB and Orb2 PLDs. However, while prior to aggregation the Orb2 PLD monomer remains mainly as a random coil in solution, ApCPEB PLD adopts a diversity of conformations comprising α-helical structures that evolve to coiled-coil species, indicating structural differences at the beginning of their amyloid assembly pathways. Conclusion: Our results indicate that divergent PLDs of CPEB proteins from different species retain the ability to form a generic amyloid-like fold through different assembly mechanisms.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcbiol/-
dc.relation.ispartofBMC Biology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCytoplasmic polyadenylation element binding protein (CPEB)-
dc.subjectFunctional amyloids-
dc.subjectPrion-like protein-
dc.subjectMemory persistence-
dc.subjectCoiled coil-
dc.titleDivergent CPEB prion-like domains reveal different assembly mechanisms for a generic amyloid-like fold-
dc.typeArticle-
dc.identifier.emailHervás, R: ruhm@hku.hk-
dc.identifier.authorityHervás, R=rp02810-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s12915-021-00967-9-
dc.identifier.pmid33706787-
dc.identifier.pmcidPMC7953810-
dc.identifier.scopuseid_2-s2.0-85102448275-
dc.identifier.hkuros322415-
dc.identifier.volume19-
dc.identifier.spagearticle no. 43-
dc.identifier.epagearticle no. 43-
dc.identifier.isiWOS:000628849100001-
dc.publisher.placeUnited Kingdom-

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