Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in <italic toggle="yes">Archaea</italic>

ABSTRACT 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 activi...

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Autores principales:	Xian Fu, Zachary Adams, Rui Liu, Nathaniel L. Hepowit, Yifei Wu, Connor F. Bowmann, Jackob Moskovitz, Julie A. Maupin-Furlow
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	archaea methionine sulfoxide reductase oxidative stress posttranslational modification protein repair ubiquitination Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e51276bc92f4461cb45d99c28d7b0d4b
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spelling	oai:doaj.org-article:e51276bc92f4461cb45d99c28d7b0d4b2021-11-15T15:51:50ZMethionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in <italic toggle="yes">Archaea</italic>10.1128/mBio.01169-172150-7511https://doaj.org/article/e51276bc92f4461cb45d99c28d7b0d4b2017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01169-17https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Proteins that are damaged by oxidative stress are often targeted for proteolysis by the ubiquitin-proteasome system (UPS). The mechanisms that control this response are poorly understood, especially under conditions of mild oxidative stress when protein damage is modest. Here, we discovered a novel function of archaeal MsrA in guiding the Ubl modification of target proteins in the presence of mild oxidant. This newly reported activity of MsrA is distinct from its stereospecific reduction of methionine-S-sulfoxide to methionine residues. Our results are significant steps forward, first, in elucidating a protein factor that guides Ubl modification in archaea, and second, in providing an insight into oxidative stress responses that can trigger Ubl modification in a cell.Xian FuZachary AdamsRui LiuNathaniel L. HepowitYifei WuConnor F. BowmannJackob MoskovitzJulie A. Maupin-FurlowAmerican Society for Microbiologyarticlearchaeamethionine sulfoxide reductaseoxidative stressposttranslational modificationprotein repairubiquitinationMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	archaea methionine sulfoxide reductase oxidative stress posttranslational modification protein repair ubiquitination Microbiology QR1-502
spellingShingle	archaea methionine sulfoxide reductase oxidative stress posttranslational modification protein repair ubiquitination Microbiology QR1-502 Xian Fu Zachary Adams Rui Liu Nathaniel L. Hepowit Yifei Wu Connor F. Bowmann Jackob Moskovitz Julie A. Maupin-Furlow Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in <italic toggle="yes">Archaea</italic>
description	ABSTRACT 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. IMPORTANCE Proteins that are damaged by oxidative stress are often targeted for proteolysis by the ubiquitin-proteasome system (UPS). The mechanisms that control this response are poorly understood, especially under conditions of mild oxidative stress when protein damage is modest. Here, we discovered a novel function of archaeal MsrA in guiding the Ubl modification of target proteins in the presence of mild oxidant. This newly reported activity of MsrA is distinct from its stereospecific reduction of methionine-S-sulfoxide to methionine residues. Our results are significant steps forward, first, in elucidating a protein factor that guides Ubl modification in archaea, and second, in providing an insight into oxidative stress responses that can trigger Ubl modification in a cell.
format	article
author	Xian Fu Zachary Adams Rui Liu Nathaniel L. Hepowit Yifei Wu Connor F. Bowmann Jackob Moskovitz Julie A. Maupin-Furlow
author_facet	Xian Fu Zachary Adams Rui Liu Nathaniel L. Hepowit Yifei Wu Connor F. Bowmann Jackob Moskovitz Julie A. Maupin-Furlow
author_sort	Xian Fu
title	Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in <italic toggle="yes">Archaea</italic>
title_short	Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in <italic toggle="yes">Archaea</italic>
title_full	Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in <italic toggle="yes">Archaea</italic>
title_fullStr	Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in <italic toggle="yes">Archaea</italic>
title_full_unstemmed	Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in <italic toggle="yes">Archaea</italic>
title_sort	methionine sulfoxide reductase a (msra) and its function in ubiquitin-like protein modification in <italic toggle="yes">archaea</italic>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/e51276bc92f4461cb45d99c28d7b0d4b
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Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in <italic toggle="yes">Archaea</italic>

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