skip to main content

DOE PAGESDOE PAGES

Title: Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in Archaea

Methionine sulfoxide reductase A (MsrA) is an antioxidant enzyme found in all domains of life that catalyzes the reduction of methionine-S-sulfoxide (MSO) to methionine in proteins and free amino acids. We demonstrate that archaeal MsrA has a ubiquitin-like (Ubl) protein modification activity that is distinct from its stereospecific reduction of MSO residues. MsrA catalyzes this Ubl modification activity, with the Ubl-activating E1 UbaA, in the presence of the mild oxidant dimethyl sulfoxide (DMSO) and in the absence of reductant. In contrast, the MSO reductase activity of MsrA is inhibited by DMSO and requires reductant. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis reveals that MsrA-dependent Ubl conjugates are associated with DNA replication, protein remodeling, and oxidative stress and include the Ubl-modified MsrA, Orc3 (Orc1/Cdc6), and Cdc48d (Cdc48/p97 AAA+ ATPase). Overall, we found archaeal MsrA to have opposing MSO reductase and Ubl modifying activities that are associated with oxidative stress responses and controlled by exposure to mild oxidant.
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [2] ;  [3]
  1. Univ. of Florida, Gainesville, FL (United States). Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences
  2. Univ. of Kansas, Lawrence, KS (United States). Department of Pharmacology and Toxicology
  3. Univ. of Florida, Gainesville, FL (United States). Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences and Genetics Institute
Publication Date:
Grant/Contract Number:
FG02-05ER15650
Type:
Accepted Manuscript
Journal Name:
mBio (Online)
Additional Journal Information:
Journal Name: mBio (Online); Journal Volume: 8; Journal Issue: 5; Journal ID: ISSN 2150-7511
Publisher:
American Society for Microbiology
Research Org:
Univ. of Florida, Gainesville, FL (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Chemical Sciences, Geosciences & Biosciences Division
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; archaea; methionine sulfoxide reductase; oxidative stress; posttranslational modification; protein repair; ubiquitination
OSTI Identifier:
1429900