title: Dre2, a conserved eukaryotic Fe/S cluster protein, functions in cytosolic Fe/S protein biogenesis.
abstract: In a forward genetic screen for interaction with mitochondrial iron carrier proteins in Saccharomyces cerevisiae, a hypomorphic mutation of the essential DRE2 gene was found to confer lethality when combined with Delta mrs3 and Delta mrs4. The dre2 mutant or Dre2-depleted cells were deficient in cytosolic Fe/S cluster protein activities while maintaining mitochondrial Fe/S clusters. The Dre2 amino acid sequence was evolutionarily conserved, and cysteine motifs (CX(2)CXC and twin CX(2)C) in human and yeast proteins were perfectly aligned. The human Dre2 homolog (implicated in blocking apoptosis and called CIAPIN1 or anamorsin) was able to complement the nonviability of a Deltadre2 deletion strain. The Dre2 protein with triple hemagglutinin tag was located in the cytoplasm and in the mitochondrial intermembrane space. Yeast Dre2 overexpressed and purified from bacteria was brown and exhibited signature absorption and electron paramagnetic resonance spectra, indicating the presence of both [2Fe-2S] and [4Fe-4S] clusters. Thus, Dre2 is an essential conserved Fe/S cluster protein implicated in extramitochondrial Fe/S cluster assembly, similar to other components of the so-called CIA (cytoplasmic Fe/S cluster assembly) pathway although partially localized to the mitochondrial intermembrane space.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Elise R
authors.initials: ER
authors.lastname: Lyver
authors.forename: Eiko
authors.initials: E
authors.lastname: Nakamaru-Ogiso
authors.forename: Heeyong
authors.initials: H
authors.lastname: Yoon
authors.forename: Boominathan
authors.initials: B
authors.lastname: Amutha
authors.forename: Dong-Woo
authors.initials: DW
authors.lastname: Lee
authors.forename: Erfei
authors.initials: E
authors.lastname: Bi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Fevzi
authors.initials: F
authors.lastname: Daldal
authors.forename: Debkumar
authors.initials: D
authors.lastname: Pain
authors.forename: Andrew
authors.initials: A
authors.lastname: Dancis
mesh_terms: D000595:Amino Acid Sequence; D003593:Cytoplasm / Q000378:metabolism; D005057:Eukaryotic Cells; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013455:Sulfur / Q000378:metabolism*
chemical_list: C531900:Dre2 protein, S cerevisiae; D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C031127:ribosomal protein L25; D013455:Sulfur; D007501:Iron