The Elongator subunit Elp3 is a non-canonical tRNA acetyltransferase

Lin, Ting-Yu; Abbassi, Nour El Hana; Zakrzewski, Karol; Chramiec-Głąbik, Andrzej; Jemioła-Rzemińska, Małgorzata; Różycki, Jan; Glatt, Sebastian

Abstract

The Elongator complex catalyzes posttranscriptional tRNA modifications by attaching carboxy-methyl (cm5) moieties to uridine bases located in the wobble position. The catalytic subunit Elp3 is highly conserved and harbors two individual subdomains, a radical S-adenosyl methionine (rSAM) and a lysine acetyltransferase (KAT) domain. The details of its modification reaction cycle and particularly the substrate specificity of its KAT domain remain elusive. Here, we present the co-crystal structure of bacterial Elp3 (DmcElp3) bound to an acetyl-CoA analog and compare it to the structure of a monomeric archaeal Elp3 from Methanocaldococcus infernus (MinElp3). Furthermore, we identify crucial active site residues, confirm the importance of the extended N-terminus for substrate recognition and uncover the specific induction of acetyl-CoA hydrolysis by different tRNA species. In summary, our results establish the clinically relevant Elongator subunit as a non-canonical acetyltransferase and genuine tRNA modification enzyme.

• Journal Article Type: Article
• Acceptance Date: Jan 18, 2019
• Online Publication Date: Feb 7, 2019
• Publication Date: 2019
• Deposit Date: Nov 2, 2023
• Journal: Nature Communications
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 1
• DOI: https://doi.org/10.1038/s41467-019-08579-2
• Keywords: General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry; Multidisciplinary
• Public URL: https://durham-repository.worktribe.com/output/1875322
• Publisher URL: https://www.nature.com/articles/s41467-019-08579-2
• Additional Information: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).