title: RepA-WH1 prionoid: Clues from bacteria on factors governing phase transitions in amyloidogenesis.
abstract: 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.
authors.affiliation: a Department of Cellular & Molecular Biology , Centro de Investigaciones Biológicas - CSIC , Madrid , Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Giraldo
authors.affiliation: a Department of Cellular & Molecular Biology , Centro de Investigaciones Biológicas - CSIC , Madrid , Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández
authors.affiliation: a Department of Cellular & Molecular Biology , Centro de Investigaciones Biológicas - CSIC , Madrid , Spain.
authors.forename: María
authors.initials: M
authors.lastname: Moreno-del Álamo
authors.affiliation: a Department of Cellular & Molecular Biology , Centro de Investigaciones Biológicas - CSIC , Madrid , Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Molina-García
authors.affiliation: a Department of Cellular & Molecular Biology , Centro de Investigaciones Biológicas - CSIC , Madrid , Spain.
authors.forename: Aída
authors.initials: A
authors.lastname: Revilla-García
authors.affiliation: a Department of Cellular & Molecular Biology , Centro de Investigaciones Biológicas - CSIC , Madrid , Spain.
authors.forename: María Cruz
authors.initials: MC
authors.lastname: Sánchez-Martínez
authors.affiliation: a Department of Cellular & Molecular Biology , Centro de Investigaciones Biológicas - CSIC , Madrid , Spain.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Giménez-Abián
authors.affiliation: a Department of Cellular & Molecular Biology , Centro de Investigaciones Biológicas - CSIC , Madrid , Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Moreno-Díaz de la Espina
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D004265:DNA Helicases / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D004269:DNA, Bacterial; D018840:HSP70 Heat-Shock Proteins; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D000072417:Protein Domains; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000682:Amyloid; D004269:DNA, Bacterial; D018840:HSP70 Heat-Shock Proteins; D011328:Prions; D015534:Trans-Activators; C045264:replication initiator protein; D004265:DNA Helicases
keywords: Hsp70 chaperone; RepA-WH1; amyloid polymorphism; amyloid proteinopathy; bacterial prionoid; phase transitions