title: The deca-GX3 proteins Yae1-Lto1 function as adaptors recruiting the ABC protein Rli1 for iron-sulfur cluster insertion.
abstract: Cytosolic and nuclear iron-sulfur (Fe-S) proteins are involved in many essential pathways including translation and DNA maintenance. Their maturation requires the cytosolic Fe-S protein assembly (CIA) machinery. To identify new CIA proteins we employed systematic protein interaction approaches and discovered the essential proteins Yae1 and Lto1 as binding partners of the CIA targeting complex. Depletion of Yae1 or Lto1 results in defective Fe-S maturation of the ribosome-associated ABC protein Rli1, but surprisingly no other tested targets. Yae1 and Lto1 facilitate Fe-S cluster assembly on Rli1 in a chain of binding events. Lto1 uses its conserved C-terminal tryptophan for binding the CIA targeting complex, the deca-GX3 motifs in both Yae1 and Lto1 facilitate their complex formation, and Yae1 recruits Rli1. Human YAE1D1 and the cancer-related ORAOV1 can replace their yeast counterparts demonstrating evolutionary conservation. Collectively, the Yae1-Lto1 complex functions as a target-specific adaptor that recruits apo-Rli1 to the generic CIA machinery.
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany.
authors.forename: Viktoria Désirée
authors.initials: VD
authors.lastname: Paul
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mühlenhoff
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stümpfig
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Seebacher
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Karl G
authors.identifier: http://orcid.org/0000-0003-2342-7472
authors.initials: KG
authors.lastname: Kugler
authors.affiliation: Fachbereich Biologie/Genetik, Philipps-Universität Marburg, Marburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Renicke
authors.affiliation: Fachbereich Biologie/Genetik, Philipps-Universität Marburg, Marburg, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Taxis
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gavin
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Pierik
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany.
authors.forename: Roland
authors.identifier: http://orcid.org/0000-0002-8345-6518
authors.initials: R
authors.lastname: Lill
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005816:Genetic Complementation Test; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007501:Iron / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000606406:Lto1 protein, S cerevisiae; C492990:RLI1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C000606407:Yae1 protein, S cerevisiae; D013455:Sulfur; D007501:Iron
keywords: CIA machinery; S. cerevisiae; biochemistry; cell biology; human; iron-sulfur protein biogenesis; metal biology; mitochondria; post-translational modification