Divergent CPEB prion-like domains reveal different assembly mechanisms for a generic amyloid-like fold
| Autor: | Mari Suzuki, Douglas V. Laurents, Albert Galera-Prat, Yoshitaka Nagai, Mariano Carrión-Vázquez, Marta Bruix, Margarita Menéndez, Rubén Hervás, María del Carmen Fernández-Ramírez |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III |
| Rok vydání: | 2021 |
| Předmět: |
Gene isoform
Amyloid Memory persistence Polyadenylation Physiology Prions Plant Science General Biochemistry Genetics and Molecular Biology CPEB Structural Biology Aplysia Animals Prion protein lcsh:QH301-705.5 Coiled coil Ecology Evolution Behavior and Systematics Functional amyloids biology Chemistry Prion-like protein Translation (biology) Cell Biology biology.organism_classification In vitro Random coil Cell biology lcsh:Biology (General) Cytoplasm biology.protein Biophysics Protein quaternary structure General Agricultural and Biological Sciences Cytoplasmic polyadenylation element binding protein (CPEB) Developmental Biology Biotechnology Research Article |
| Zdroj: | Digital.CSIC: Repositorio Institucional del CSIC Consejo Superior de Investigaciones Científicas (CSIC) BMC Biology BMC Biology, Vol 19, Iss 1, Pp 1-14 (2021) Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 14 pags., 4 figs. Background: 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. The work was funded by two joint grants from the Ministry of Economy and Competitiveness to MCV (SAF2013-49179-C2-1-R and SAF2016-76678-C2-1-R) and DVL (SAF2013-49179-C2-2-R and SAF2016-76678-C2-2-R) and grants of the Ministry of Economy and Science (BFU2015-70072-R) and the CIBER de Enfermedades Respiratorias (CIBERES; ISCIII) to MM. |
| Databáze: | OpenAIRE |
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