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

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 U...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574740/
https://www.ncbi.nlm.nih.gov/pubmed/36102610
http://dx.doi.org/10.15252/embj.2022111318
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author 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
author_facet 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
author_sort Ravichandran, Keerthiraju E
collection PubMed
description 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.
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spelling pubmed-95747402022-10-26 E2/E3‐independent ubiquitin‐like protein conjugation by Urm1 is directly coupled to cysteine persulfidation 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 EMBO J Articles 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. John Wiley and Sons Inc. 2022-09-14 /pmc/articles/PMC9574740/ /pubmed/36102610 http://dx.doi.org/10.15252/embj.2022111318 Text en © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
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
E2/E3‐independent ubiquitin‐like protein conjugation by Urm1 is directly coupled to cysteine persulfidation
title E2/E3‐independent ubiquitin‐like protein conjugation by Urm1 is directly coupled to cysteine persulfidation
title_full E2/E3‐independent ubiquitin‐like protein conjugation by Urm1 is directly coupled to cysteine persulfidation
title_fullStr E2/E3‐independent ubiquitin‐like protein conjugation by Urm1 is directly coupled to cysteine persulfidation
title_full_unstemmed E2/E3‐independent ubiquitin‐like protein conjugation by Urm1 is directly coupled to cysteine persulfidation
title_short E2/E3‐independent ubiquitin‐like protein conjugation by Urm1 is directly coupled to cysteine persulfidation
title_sort e2/e3‐independent ubiquitin‐like protein conjugation by urm1 is directly coupled to cysteine persulfidation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574740/
https://www.ncbi.nlm.nih.gov/pubmed/36102610
http://dx.doi.org/10.15252/embj.2022111318
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