Rafael Giraldo - Major publications#

(For a COMPLETE LIST: https://scholar.google.es/citations?user=a3LDW28AAAAJ&hl=es&oi=ao)

GIRALDO R, Nieto C, Fernandez-Tresguerres ME, Diaz R (1989) Bacterial zipper. Nature 342: 866.
This brief note was the pioneering description of a LZ motif in a prokaryotic protein and the frst insight on the structure of any plasmid replication protein.

GIRALDO R, Rhodes D (1994) The yeast telomere-binding protein RAP1 binds to and promotes the formation of DNA-quadruplexes in telomeric DNA. EMBO J. 13: 2411-2420.
One of the very first chaperoning activities reported for a protein (Rapl) on DNA folding (assembly of four-stranded helices). Still quoted often as a landmark in the research on an increasing number of proteins dealing with G4-DNA, relevant for telomere structure.

GIRALDO R, Suzuki M, Chapman L, Rhodes D (1994) Promotion of parallel DNA quadruplexes by a yeast telomere binding protein: A circular dichroism study. Proc. Natl. Acad Sci. USA 91: 7658- 7662.
This paper is frequently cited today as a seminal reference on the use of CD spectroscopy to study the structure and assembly of G4-DNA.

Rhodes D, GIRALDO R (1995) Telomere structure and function. Curr. Op. Struct. Biol. 5: 311-322 (review article).
This is still an insighdul view on the function of G4-DNA binding proteins. Our papers inspired much ofthe current work on telomerase inhibitors targeting G4-DNA.

König P.*, GIRALDO R.*, Chapman L, Rhodes D (1996) The crystal structure of the DNA binding domain of yeast RAP1 in complex with a telomeric DNA site. Cell 85: 125-136.
(*: equally contributing authors).
This is the first 3D-structure solved for a protein-DNA telomeric complex. It has proven to be key for understanding how is telomeric DNA recognized by homologous metazoan proteins. The structure was cover in the journal.

Del Solar G, GIRALDO R, Ruiz-Echevarria MJ, Espinosa M, Diaz-Orejas R (1998) Replication and control of circular bacterial plasmids. Microbiol. & Mol. Biol. Rev. 62: 434-464 (review article).
The most authoritative and cited review on plasmid DNA replication.

GIRALDO R, Andreu JM, Díaz-Orejas R (1998) Protein domains and conformational changes in the activation of RepA, a DNA replication initiator. EMBO J. 17: 4511-4526.
The turning point for the understanding of plasmid initiation, because it provided the first description of domains in a Rep protein and the existence of alternative conformations linked to its dimeric or monomeric functional states.

GIRALDO R, Diaz-Orejas R (2001) Similarities between the DNA replication initiators of Gram-negative bacteria plasmids (RepA) and eukaryotes (Orc4p) / archaea (Cdc6p). Proc. Natl. Acad Sci. USA. 98: 4938-4943.
Prediction of the existence of RepA-like WH domains in a subunit of ORC, the eukaryotic initiator. Seminal report on Hsp 70 chaperone-ORC interactions.

GIRALDO R, Fernandez-Tornero C, Evans PR, Diaz—Orejas R, Romero A (2003) A conformational switch between transcriptional repression and replication initiation in the RepA dimerization domain. Nat. Struct. Biol. 10: 565-571.
The crystal structure of the N-terminal WH in RepA defined the details of the structural transformation activating DNA replication and confirmed RepA similarity with ORC

GIRALDO R (2007) Defined DNA sequences promote the assembly of a bacterial protein into distinct amyloid nanostructures. Proc. Natl. Acad Sci. USA 104: 17388-17393.
Building on the grounds of our work on the structural transformation of RepA, this paper describes how this protein behaves as the mammalian prion PrP, by assembling into amyloids upon DNA binding. This is the first fully bacterial model system for prion amyloidosis.

Gasset-Rosa F, Coquel AS, Moreno-del Álamo M, Chen P, Song X, Serrano AM, Fernández-Tresguerres ME, Moreno-Díaz de la Espina S, Lindner AB, GIRALDO R (2014) Direct assessment in bacteria of prionoid propagation and phenotype selection by Hsp70 chaperone. Mol. Microbiol. 91: 1070-1087.
Two different amyloid strains were identified in the RepA-WH1 prionoid in E. coli: either globular (G; cytotoxic) or comet-shaped (C; with reduced toxicity). DnaK, an Hsp70 chaperone, displaces the equilibrium towards C, linking these strains with the conformational (folding and aggregation) landscape of RepA-WH1.

Fernández C, Núñez-Ramírez R, Jiménez M, Rivas G, GIRALDO R (2016) RepA-WH1, the agent of an amyloid proteinopathy in bacteria, builds oligomeric pores through lipid vesicles. Sci. Rep. 6: 23144.
The bacterial prionoid RepA-WH1 aggregates in vitro on the surface of lipid vesicles enriched in acidic phospholipids, assembling oligomeric pores through which encapsulated, intravesicular small molecules leak. This behavior mimics membrane targeting by amyloidogneic proteins relevant to human neurodegenerative diseases.

Molina-García L, Gasset-Rosa F, Moreno-del Álamo M, Fernández-Tresguerres ME, Moreno-Díaz de la Espina S, Lurz R, GIRALDO R (2016) Functional amyloids as inhibitors of plasmid DNA replication. "Sci. Rep."6: 25425.
RepA as the first bacterial intracellular functional amyloid, negatively controlling plasmid DNA replication.

Molina-García L, Moreno-del Álamo M, Botias P, Martín-Moldes Z, Fernández M, Sánchez-Gorostiaga A, Alonso-del Valle A, Nogales J, García-Cantalejo J, GIRALDO R (2017) RepA-WH1, the agent of an amyloid proteinopathy in bacteria, builds oligomeric pores through lipid vesicleOutlining core pathways of amyloid toxicity in bacteria with the RepA-WH1 prionoid. Front. Microbiol. 8: 539.
The stroke to the inner bacterial membrane by RepA-WH1 decreases the levels of Fe and ATP and induces NdhII dehydrogenase, which generates H2O2 thus triggering oxidative stress. Co-aggregation of stress-responsive factors leaves bacteria defenceless. Similar routes are likely involved in damage to mitochondria in human amyloidoses.

GIRALDO R (2019) Optogenetic navigation of routes leading to protein amyloidogenesis in bacteria. J. Mol. Biol. 431: 1186-1202.
Synthetic devices built on chimeras between a plant photorreceptor (LOV2) and amyloidogenic RepA-WH1 enable light-tuned control of amyloid cytotoxicity in bacteria.

Revilla-García A, Fernández C, Moreno-del Álamo M, de los Ríos V, Vorberg IM, GIRALDO R (2020) Intercellular transmission of a synthetic bacterial cytotoxic prion-like protein in mammalian cells. mBio 11: e02937-19.
Horizontal propagation of prion-like RepA-WH1 in mammalian cells is solely possible if recipient cells express the bacterial protein: This seeds amyloid aggregation and triggers cytotoxicity routes with a central target in mitochondria.

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