Abstract

Protein S-persulfidation (P-SSH) is recognized as a common posttranslational modification. It occurs under basal conditions and is often observed to be elevated under stress conditions. However, the mechanism(s) by which proteins are persulfidated inside cells have remained unclear. Here we report that 3-mercaptopyruvate sulfur transferase (MPST) engages in direct protein-to-protein transpersulfidation reactions beyond its previously known protein substrates thioredoxin and MOCS3/Uba4, associated with H2S generation and transfer RNA thiolation, respectively. We observe that depletion of MPST in human cells lowers overall intracellular protein persulfidation levels and identify a subset of proteins whose persulfidation depends on MPST. The predicted involvement of these proteins in the adaptation to stress responses supports the notion that MPST-dependent protein persulfidation promotes cytoprotective functions. The observation of MPST-independent protein persulfidation suggests that other protein persulfidases remain to be identified.

Mercaptopyruvate sulfur transferase (MPST) is revealed as a protein persulfidase that acts directly on numerous and diverse target proteins, revealing potential origins of persulfidation as a common posttranslational modification.

Details

Title
3-Mercaptopyruvate sulfur transferase is a protein persulfidase
Author
Pedre, Brandán 1   VIAFID ORCID Logo  ; Talwar, Deepti 1   VIAFID ORCID Logo  ; Barayeu, Uladzimir 2   VIAFID ORCID Logo  ; Schilling, Danny 2 ; Luzarowski, Marcin 3 ; Sokolowski, Mikolaj 4 ; Glatt, Sebastian 4   VIAFID ORCID Logo  ; Dick, Tobias P. 2   VIAFID ORCID Logo 

 Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany (GRID:grid.509524.f) 
 Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany (GRID:grid.509524.f); Heidelberg University, Faculty of Biosciences, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373) 
 Core Facility for Mass Spectrometry and Proteomics, Centre for Molecular Biology at Heidelberg University (ZMBH), Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373) 
 Jagiellonian University, Max Planck Research Group, Malopolska Centre of Biotechnology, Kraków, Poland (GRID:grid.5522.0) (ISNI:0000 0001 2162 9631) 
Pages
507-517
Publication year
2023
Publication date
Apr 2023
Publisher
Nature Publishing Group
ISSN
15524450
e-ISSN
15524469
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2792243503
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.