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Nat Struct Mol Biol. 2016 Sep;23(9):794-802. doi: 10.1038/nsmb.3265. Epub 2016 Jul 25.

Structural basis for tRNA modification by Elp3 from Dehalococcoides mccartyi.

Author information

1
European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
2
Max Planck Research Group at the Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
3
Institute of Biology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
4
Université de Strasbourg, IGBMC UMR 7104, Illkirch, France.
5
CNRS, IGBMC UMR 7104, Illkirch, France.
6
Inserm, IGBMC U964, Illkirch, France.
7
Unit of Virus Host-Cell Interactions (UMI 3265), University Grenoble Alpes-CNRS-EMBL, Grenoble, France.
8
Laboratoire de Bioénergétique et Ingénierie des Protéines, BIP/CNRS, UMR7281, AMU, Marseille, France.
#
Contributed equally

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.

PMID:
27455459
PMCID:
PMC5018218
DOI:
10.1038/nsmb.3265
[Indexed for MEDLINE]
Free PMC Article

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