Ravichandran, Keerthiraju E; Kaduhr, Lars; Skupien-Rabian, Bozena; Shvetsova, Ekaterina; Sokołowski, Mikołaj; Krutyhołowa, Ros Cisław; Kwasna, Dominika; Brachmann, Cindy; Lin, Sean; Guzman Perez, Sebastian; Wilk, Piotr; Kösters, Manuel; Grudnik, Przemysław; Jankowska, Urszula; Leidel, Sebastian A; Schaffrath, Raffael; Glatt, Sebastian (2022). E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation. The EMBO journal, 41(20), e111318. EMBO Press 10.15252/embj.2022111318
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The_EMBO_Journal_-_2022_-_Ravichandran_-_E2_E3_independent_ubiquitin_like_protein_conjugation_by_Urm1_is_directly_coupled.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (3MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Shvetsova, Ekaterina, Kösters, Manuel, Leidel, Sebastian Andreas |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
1460-2075 |
Publisher: |
EMBO Press |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
22 Sep 2022 09:21 |
Last Modified: |
05 Dec 2022 16:24 |
Publisher DOI: |
10.15252/embj.2022111318 |
PubMed ID: |
36102610 |
Uncontrolled Keywords: |
Urm1 oxidative stress persulfidation sulfur transfer ubiquitin-like |
BORIS DOI: |
10.48350/173059 |
URI: |
https://boris.unibe.ch/id/eprint/173059 |
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