title: Structural basis for tRNA modification by Elp3 from Dehalococcoides mccartyi.
abstract: During translation elongation, decoding is based on the recognition of codons by corresponding tRNA anticodon triplets. Molecular mechanisms that regulate global protein synthesis via specific base modifications in tRNA anticodons are receiving increasing attention. The conserved eukaryotic Elongator complex specifically modifies uridines located in the wobble base position of tRNAs. Mutations in Elongator subunits are associated with certain neurodegenerative diseases and cancer. Here we present the crystal structure of D. mccartyi Elp3 (DmcElp3) at 2.15-Å resolution. Our results reveal an unexpected arrangement of Elp3 lysine acetyltransferase (KAT) and radical S-adenosyl methionine (SAM) domains, which share a large interface and form a composite active site and tRNA-binding pocket, with an iron-sulfur cluster located in the dimerization interface of two DmcElp3 molecules. Structure-guided mutagenesis studies of yeast Elp3 confirmed the relevance of our findings for eukaryotic Elp3s and should aid in understanding the cellular functions and pathophysiological roles of Elongator.
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.|Max Planck Research Group at the Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Glatt
authors.affiliation: Institute of Biology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Rene
authors.initials: R
authors.lastname: Zabel
authors.affiliation: Université de Strasbourg, IGBMC UMR 7104, 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: Institute of Biology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Osita F
authors.initials: OF
authors.lastname: Onuma
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.|Unit of Virus Host-Cell Interactions (UMI 3265), University Grenoble Alpes-CNRS-EMBL, Grenoble, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Baudin
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Graziadei
authors.affiliation: Université de Strasbourg, IGBMC UMR 7104, Illkirch, France.|CNRS, IGBMC UMR 7104, Illkirch, France.|Inserm, IGBMC U964, Illkirch, France.
authors.forename: Valerio
authors.initials: V
authors.lastname: Taverniti
authors.affiliation: Max Planck Research Group at the Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Laboratoire de Bioénergétique et Ingénierie des Protéines, BIP/CNRS, UMR7281, AMU, Marseille, France.
authors.forename: Frauke
authors.initials: F
authors.lastname: Baymann
authors.affiliation: Université de Strasbourg, IGBMC UMR 7104, Illkirch, France.|CNRS, IGBMC UMR 7104, Illkirch, France.|Inserm, IGBMC U964, Illkirch, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Seraphin
authors.affiliation: Institute of Biology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Karin D
authors.initials: KD
authors.lastname: Breunig
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Müller
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D041862:Chloroflexi / Q000201:enzymology; D018360:Crystallography, X-Ray; D051548:Histone Acetyltransferases / Q000737:chemistry*; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D055503:Protein Multimerization; D012329:RNA, Bacterial / Q000737:chemistry; D012343:RNA, Transfer / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D012343:RNA, Transfer; D051548:Histone Acetyltransferases