title: Interaction between the reductase Tah18 and highly conserved Fe-S containing Dre2 C-terminus is essential for yeast viability.
abstract: Tah18-Dre2 is a recently identified yeast protein complex, which is highly conserved in human and has been implicated in the regulation of oxidative stress induced cell death and in cytosolic Fe-S proteins synthesis. Tah18 is a diflavin oxido-reductase with binding sites for flavin mononucleotide, flavin adenine dinucleotide and nicotinamide adenine dinucleotide phosphate, which is able to transfer electrons to Dre2 Fe-S clusters. In this work we characterized in details the interaction between Tah18 and Dre2, and analysed how it conditions yeast viability. We show that Dre2 C-terminus interacts in vivo and in vitro with the flavin mononucleotide- and flavin adenine dinucleotide-binding sites of Tah18. Neither the absence of the electron donor nicotinamide adenine dinucleotide phosphate-binding domain in purified Tah18 nor the absence of Fe-S in aerobically purified Dre2 prevents the binding in vitro. In vivo, when this interaction is affected in a dre2 mutant, yeast viability is reduced. Conversely, enhancing artificially the interaction between mutated Dre2 and Tah18 restores cellular viability despite still reduced cytosolic Fe-S cluster biosynthesis. We conclude that Tah18-Dre2 interaction in vivo is essential for yeast viability. Our study may provide new insight into the survival/death switch involving this complex in yeast and in human cells.
authors: CNRS UMR2027 Institut Curie Centre de Recherche, Centre Universitaire, 91405 Orsay, France.
authors: Nicolas
authors: N
authors: Soler
authors: Emmanuelle
authors: E
authors: Delagoutte
authors: Simona
authors: S
authors: Miron
authors: Céline
authors: C
authors: Facca
authors: Dorothée
authors: D
authors: Baïlle
authors: Benoit
authors: B
authors: d'Autreaux
authors: Gil
authors: G
authors: Craescu
authors: Yves-Michel
authors: YM
authors: Frapart
authors: Daniel
authors: D
authors: Mansuy
authors: Giuseppe
authors: G
authors: Baldacci
authors: Meng-Er
authors: ME
authors: Huang
authors: Laurence
authors: L
authors: Vernis
mesh_terms: D005486:Flavin Mononucleotide / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D050296:Microbial Viability; D010088:Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: C531900:Dre2 protein, S cerevisiae; D007506:Iron-Sulfur Proteins; D029701:Saccharomyces cerevisiae Proteins; D005182:Flavin-Adenine Dinucleotide; D005486:Flavin Mononucleotide; D010088:Oxidoreductases; C552878:Tah18 protein, S cerevisiae