RepA-WH1 prionoid: Clues from bacteria on factors governing phase transitions in amyloidogenesis.
In bacterial plasmids, Rep proteins initiate DNA replication by undergoing a structural transformation coupled to dimer dissociation. Amyloidogenesis of the 'winged-helix' N-terminal domain of RepA (WH1) is triggered in vitro upon binding to plasmid-specific DNA sequences, and occurs at the bacterial nucleoid in vivo. Amyloid fibers are made of distorted RepA-WH1 monomers that assemble as single or double intertwined tubular protofilaments. RepA-WH1 causes in E. coli an amyloid proteinopathy, which is transmissible from mother to daughter cells, but not infectious, and enables conformational imprinting in vitro and in vivo; i.e. RepA-WH1 is a 'prionoid'. Microfluidics allow the assessment of the intracellular dynamics of RepA-WH1: bacterial lineages maintain two types (strains-like) of RepA-WH1 amyloids, either multiple compact cytotoxic particles or a single aggregate with the appearance of a fluidized hydrogel that it is mildly detrimental to growth. The Hsp70 chaperone DnaK governs the phase transition between both types of RepA-WH1 aggregates in vivo, thus modulating the vertical propagation of the prionoid. Engineering chimeras between the Sup35p/[PSI(+)] prion and RepA-WH1 generates [REP-PSI(+)], a synthetic prion exhibiting strong and weak phenotypic variants in yeast. These recent findings on a synthetic, self-contained bacterial prionoid illuminate central issues of protein amyloidogenesis.
['Giraldo|Rafael|R|', 'Fernández|Cristina|C|', 'Moreno-del Álamo|María|M|', 'Molina-García|Laura|L|', 'Revilla-García|Aída|A|', 'Sánchez-Martínez|María Cruz|MC|', 'Giménez-Abián|Juan F|JF|', 'Moreno-Díaz de la Espina|Susana|S|']
D000682:Amyloid D004265:DNA Helicases D004269:DNA, Bacterial D018840:HSP70 Heat-Shock Proteins D011328:Prions D011487:Protein Conformation D000072417:Protein Domains D015534:Trans-Activators
RepA-WH1 phase transitions amyloid proteinopathy Hsp70 chaperone bacterial prionoid amyloid polymorphism