Journal Article Research Support, Non-U.S. Gov't Ppublish 10 citations
PubMed: 36102610 DOI: 10.15252/embj.2022111318
E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation.
EMBO J 41(20):e111318
Authors: Keerthiraju E Ravichandran, Lars Kaduhr, Bozena Skupien-Rabian, Ekaterina Shvetsova, Mikołaj Sokołowski, Rościsław Krutyhołowa, Dominika Kwasna, Cindy Brachmann, Sean Lin, Sebastian Guzman Perez, Piotr Wilk, Manuel Kösters, Przemysław Grudnik, Urszula Jankowska, Sebastian A Leidel, Raffael Schaffrath, Sebastian Glatt
Affiliations
- Malopolska Centre of Biotechnology (MCB), Jagiellonian University, Krakow, Poland.
- Postgraduate School of Molecular Medicine, Warsaw, Poland.
- Department for Microbiology, Institute for Biology, University of Kassel, Kassel, Germany.
- Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.
- Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, Bern, Switzerland.
- Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
- Max Planck Institute of Biochemistry, Martinsried, Germany.
- Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland. Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, Bern, Switzerland.
Abstract
Post-translational modifications by ubiquitin-like proteins (UBLs) are essential for nearly all cellular processes. Ubiquitin-related modifier 1 (Urm1) is a unique UBL, which plays a key role in tRNA anticodon thiolation as a sulfur carrier protein (SCP) and is linked to the noncanonical E1 enzyme Uba4 (ubiquitin-like protein activator 4). While Urm1 has also been observed to conjugate to target proteins like other UBLs, the molecular mechanism of its attachment remains unknown. Here, we reconstitute the covalent attachment of thiocarboxylated Urm1 to various cellular target proteins in vitro, revealing that, unlike other known UBLs, this process is E2/E3-independent and requires oxidative stress. Furthermore, we present the crystal structures of the peroxiredoxin Ahp1 before and after the covalent attachment of Urm1. Surprisingly, we show that urmylation is accompanied by the transfer of sulfur to cysteine residues in the target proteins, also known as cysteine persulfidation. Our results illustrate the role of the Uba4-Urm1 system as a key evolutionary link between prokaryotic SCPs and the UBL modifications observed in modern eukaryotes.
MeSH
Cysteine, Ubiquitin, Oxidative Stress
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- E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation. EMBO J, 2022