MassIVE MSV000088390

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E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation

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Description

Posttranslational modifications by ubiquitin-like proteins (UBL) are essential for nearly all cellular processes. Ubiquitin related modifier 1 (Urm1) is a non-canonical UBL which plays a key role in tRNA anticodon thiolation as a sulfur carrier protein (SCP). While Urm1 has also been observed to conjugate directly to target proteins like other UBLs, the mechanism of attachment as well as how the SCP properties of Urm1 may impact its conjugation are unknown. Here, we reconstitute the covalent attachment of Urm1 to various cellular target proteins in vitro, revealing that, unlike other known UBLs, this process is E2/E3-independent and requires oxidative stress conditions. We determined the crystal structures of the peroxiredoxin Ahp1 before and after covalent attachment of Urm1. Strikingly, we show that this conjugation process results in persulfidation of a cysteine residue in the target protein. Demonstrating that Urm1 actively transfers sulfur atoms to proteins as part of its conjugation reaction. Our results redefine Urm1 as a key evolutionary link between prokaryotic SCPs and the plethora of UBL modifications observed in modern eukaryotes, and demonstrate a critical role for Urm1 in protecting proteins during oxidative stress. [doi:10.25345/C59Z9C] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Urm1 ; sulfur transfer ; ubiquitin-like ; persulfidation ; oxidative stress

Contact

Principal Investigators:
(in alphabetical order) 		Sebastian Glatt, Malopolska Centre of Biotechnology (MCB), Jagiellonian University, Poland
Submitting User: Urszula

Publications

Ravichandran KE, Kaduhr L, Skupien-Rabian B, Shvetsova E, Soko?owski M, Krutyho?owa RC, Kwasna D, Brachmann C, Lin S, Guzman Perez S, Wilk P, Kösters M, Grudnik P, Jankowska U, Leidel SA, Schaffrath R, Glatt S.
E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation.
EMBO J. 2022 Oct 17;41(20):e111318. Epub 2022 Sep 14.

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