title: Architecture of the yeast Elongator complex.
abstract: The highly conserved eukaryotic Elongator complex performs specific chemical modifications on wobble base uridines of tRNAs, which are essential for proteome stability and homeostasis. The complex is formed by six individual subunits (Elp1-6) that are all equally important for its tRNA modification activity. However, its overall architecture and the detailed reaction mechanism remain elusive. Here, we report the structures of the fully assembled yeast Elongator and the Elp123 sub-complex solved by an integrative structure determination approach showing that two copies of the Elp1, Elp2, and Elp3 subunits form a two-lobed scaffold, which binds Elp456 asymmetrically. Our topological models are consistent with previous studies on individual subunits and further validated by complementary biochemical analyses. Our study provides a structural framework on how the tRNA modification activity is carried out by Elongator.
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Dauden
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kosinski
authors.affiliation: Université de Strasbourg, IGBMC, Illkirch, France.|CNRS, IGBMC UMR 7104, Illkirch, France.|Inserm, IGBMC U964, Illkirch, France.
authors.forename: Olga
authors.initials: O
authors.lastname: Kolaj-Robin
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Ambroise
authors.initials: A
authors.lastname: Desfosses
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ori
authors.affiliation: Université de Strasbourg, IGBMC, Illkirch, France.|CNRS, IGBMC UMR 7104, Illkirch, France.|Inserm, IGBMC U964, Illkirch, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Faux
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Niklas A
authors.initials: NA
authors.lastname: Hoffmann
authors.affiliation: Institute of Biology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Osita F
authors.initials: OF
authors.lastname: Onuma
authors.affiliation: Institute of Biology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Karin D
authors.identifier: 0000-0002-0319-3114
authors.initials: KD
authors.lastname: Breunig
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Martin
authors.identifier: 0000-0002-7397-1321
authors.initials: M
authors.lastname: Beck
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Carsten
authors.identifier: 0000-0002-1168-5143
authors.initials: C
authors.lastname: Sachse
authors.affiliation: Université de Strasbourg, IGBMC, Illkirch, France.|CNRS, IGBMC UMR 7104, Illkirch, France.|Inserm, IGBMC U964, Illkirch, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Séraphin
authors.affiliation: Max Planck Research Group at the Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland sebastian.glatt@uj.edu.pl cmueller@embl.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Glatt
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany sebastian.glatt@uj.edu.pl cmueller@embl.de.
authors.forename: Christoph W
authors.identifier: 0000-0003-2176-8337
authors.initials: CW
authors.lastname: Müller
mesh_terms: D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D005656:Fungal Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins
keywords: 
  Saccharomyces cerevisiae
  ; Elongator; electron microscopy; tRNA modification; yeast