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

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.

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:
Research Org.:
Univ. of Florida, Gainesville, FL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences, and Biosciences Division
OSTI Identifier:
1429900
Grant/Contract Number:  
FG02-05ER15650
Resource 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
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

Citation Formats

Fu, Xian, Adams, Zachary, Liu, Rui, Hepowit, Nathaniel L., Wu, Yifei, Bowmann, Connor F., Moskovitz, Jackob, and Maupin-Furlow, Julie A. Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in Archaea. United States: N. p., 2017. Web. doi:10.1128/mBio.01169-17.
Fu, Xian, Adams, Zachary, Liu, Rui, Hepowit, Nathaniel L., Wu, Yifei, Bowmann, Connor F., Moskovitz, Jackob, & Maupin-Furlow, Julie A. Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in Archaea. United States. https://doi.org/10.1128/mBio.01169-17
Fu, Xian, Adams, Zachary, Liu, Rui, Hepowit, Nathaniel L., Wu, Yifei, Bowmann, Connor F., Moskovitz, Jackob, and Maupin-Furlow, Julie A. Tue . "Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in Archaea". United States. https://doi.org/10.1128/mBio.01169-17. https://www.osti.gov/servlets/purl/1429900.
@article{osti_1429900,
title = {Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in Archaea},
author = {Fu, Xian and Adams, Zachary and Liu, Rui and Hepowit, Nathaniel L. and Wu, Yifei and Bowmann, Connor F. and Moskovitz, Jackob and Maupin-Furlow, Julie A.},
abstractNote = {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.},
doi = {10.1128/mBio.01169-17},
journal = {mBio (Online)},
number = 5,
volume = 8,
place = {United States},
year = {Tue Sep 05 00:00:00 EDT 2017},
month = {Tue Sep 05 00:00:00 EDT 2017}
}

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Works referenced in this record:

Cloning the expression of a mammalian gene involved in the reduction of methionine sulfoxide residues in proteins.
journal, March 1996

  • Moskovitz, J.; Weissbach, H.; Brot, N.
  • Proceedings of the National Academy of Sciences, Vol. 93, Issue 5
  • DOI: 10.1073/pnas.93.5.2095

Inhibition of methionine sulfoxide reduction by dimethyl sulfoxide
journal, September 2009


Ubiquitin-like small archaeal modifier proteins (SAMPs) in Haloferax volcanii
journal, January 2010

  • Humbard, Matthew A.; Miranda, Hugo V.; Lim, Jae-Min
  • Nature, Vol. 463, Issue 7277
  • DOI: 10.1038/nature08659

Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide
journal, July 2014

  • Fischer, Eric S.; Böhm, Kerstin; Lydeard, John R.
  • Nature, Vol. 512, Issue 7512
  • DOI: 10.1038/nature13527

The yeast peptide-methionine sulfoxide reductase functions as an antioxidant in vivo
journal, September 1997

  • Moskovitz, J.; Berlett, B. S.; Poston, J. M.
  • Proceedings of the National Academy of Sciences, Vol. 94, Issue 18
  • DOI: 10.1073/pnas.94.18.9585

Repair, refold, recycle: how bacteria can deal with spontaneous and environmental damage to proteins
journal, June 1995


Prokaryotic Ubiquitin-Like Protein Modification
journal, September 2014


Archaeal JAB1/MPN/MOV34 metalloenzyme (HvJAMM1) cleaves ubiquitin-like small archaeal modifier proteins (SAMPs) from protein-conjugates: Archaeal JAMM isopeptidase
journal, October 2012

  • Hepowit, Nathaniel L.; Uthandi, Sivakumar; Miranda, Hugo V.
  • Molecular Microbiology, Vol. 86, Issue 4
  • DOI: 10.1111/mmi.12038

Ubiquitin–proteasome pathway and cellular responses to oxidative stress
journal, July 2011


Methionine sulfoxide reductase: Chemistry, substrate binding, recycling process and oxidase activity
journal, December 2014


A Statistical Model for Identifying Proteins by Tandem Mass Spectrometry
journal, September 2003

  • Nesvizhskii, Alexey I.; Keller, Andrew; Kolker, Eugene
  • Analytical Chemistry, Vol. 75, Issue 17
  • DOI: 10.1021/ac0341261

Mechanistic insight into protein modification and sulfur mobilization activities of noncanonical E1 and associated ubiquitin-like proteins of Archaea
journal, October 2016

  • Hepowit, Nathaniel L.; de Vera, Ian Mitchelle S.; Cao, Shiyun
  • The FEBS Journal, Vol. 283, Issue 19
  • DOI: 10.1111/febs.13819

Regulating the 20S Proteasome Ubiquitin-Independent Degradation Pathway
journal, September 2014


Identification and Characterization of a Putative Active Site for Peptide Methionine Sulfoxide Reductase (MsrA) and Its Substrate Stereospecificity
journal, May 2000

  • Moskovitz, Jackob; Poston, J. Michael; Berlett, Barbara S.
  • Journal of Biological Chemistry, Vol. 275, Issue 19
  • DOI: 10.1074/jbc.275.19.14167

[45] Escherichia coli peptide methionine sulfoxide reductase: Cloning, high expression, and purification
book, January 1995


Regulated protein turnover: snapshots of the proteasome in action
journal, January 2014

  • Bhattacharyya, Sucharita; Yu, Houqing; Mim, Carsten
  • Nature Reviews Molecular Cell Biology, Vol. 15, Issue 2
  • DOI: 10.1038/nrm3741

Structural and Functional Insights to Ubiquitin-Like Protein Conjugation
journal, May 2014


Genetic and Physical Mapping of DNA Replication Origins in Haloferax volcanii
journal, May 2007


E1- and ubiquitin-like proteins provide a direct link between protein conjugation and sulfur transfer in archaea
journal, February 2011

  • Miranda, H. V.; Nembhard, N.; Su, D.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 11
  • DOI: 10.1073/pnas.1018151108

Redox control of protein degradation
journal, December 2015


Structure of the human Cereblon–DDB1–lenalidomide complex reveals basis for responsiveness to thalidomide analogs
journal, August 2014

  • Chamberlain, Philip P.; Lopez-Girona, Antonia; Miller, Karen
  • Nature Structural & Molecular Biology, Vol. 21, Issue 9
  • DOI: 10.1038/nsmb.2874

Characterization of the Amino Acids from Neisseria meningitidis MsrA Involved in the Chemical Catalysis of the Methionine Sulfoxide Reduction Step
journal, October 2006

  • Antoine, Mathias; Gand, Adeline; Boschi-Muller, Sandrine
  • Journal of Biological Chemistry, Vol. 281, Issue 51
  • DOI: 10.1074/jbc.m608844200

Modification of Proteins by Ubiquitin and Ubiquitin-Like Proteins
journal, November 2006


Protein oxidation in aging and the removal of oxidized proteins
journal, October 2013


Empirical Statistical Model To Estimate the Accuracy of Peptide Identifications Made by MS/MS and Database Search
journal, October 2002

  • Keller, Andrew; Nesvizhskii, Alexey I.; Kolker, Eugene
  • Analytical Chemistry, Vol. 74, Issue 20
  • DOI: 10.1021/ac025747h

NIH Image to ImageJ: 25 years of image analysis
journal, June 2012

  • Schneider, Caroline A.; Rasband, Wayne S.; Eliceiri, Kevin W.
  • Nature Methods, Vol. 9, Issue 7
  • DOI: 10.1038/nmeth.2089

Proteome targets of ubiquitin-like samp1ylation are associated with sulfur metabolism and oxidative stress in Haloferax volcanii
journal, April 2016

  • Dantuluri, Swathi; Wu, Yifei; Hepowit, Nathaniel L.
  • PROTEOMICS, Vol. 16, Issue 7
  • DOI: 10.1002/pmic.201500153

Involvement of a eukaryotic-like ubiquitin-related modifier in the proteasome pathway of the archaeon Sulfolobus acidocaldarius
journal, September 2015

  • Anjum, Rana S.; Bray, Sian M.; Blackwood, John K.
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms9163

The mirrored methionine sulfoxide reductases of Neisseria gonorrhoeae pilB
journal, April 2002

  • Lowther, W. Todd; Weissbach, Herbert; Etienne, Frantzy
  • Nature Structural Biology
  • DOI: 10.1038/nsb783

Oxidative Stress Resistance in Deinococcus radiodurans
journal, March 2011

  • Slade, D.; Radman, M.
  • Microbiology and Molecular Biology Reviews, Vol. 75, Issue 1
  • DOI: 10.1128/MMBR.00015-10

Archaeal Ubiquitin-like SAMP3 is Isopeptide-linked to Proteins via a UbaA-dependent Mechanism
journal, October 2013

  • Miranda, Hugo V.; Antelmann, Haike; Hepowit, Nathaniel
  • Molecular & Cellular Proteomics, Vol. 13, Issue 1
  • DOI: 10.1074/mcp.M113.029652

Archaeal Inorganic Pyrophosphatase Displays Robust Activity under High-Salt Conditions and in Organic Solvents
journal, November 2015

  • McMillan, Lana J.; Hepowit, Nathaniel L.; Maupin-Furlow, Julie A.
  • Applied and Environmental Microbiology, Vol. 82, Issue 2
  • DOI: 10.1128/AEM.03055-15

GlpR Represses Fructose and Glucose Metabolic Enzymes at the Level of Transcription in the Haloarchaeon Haloferax volcanii
journal, October 2010

  • Rawls, K. S.; Yacovone, S. K.; Maupin-Furlow, J. A.
  • Journal of Bacteriology, Vol. 192, Issue 23
  • DOI: 10.1128/JB.00827-10

Development of a Gene Knockout System for the Halophilic Archaeon Haloferax volcanii by Use of the pyrE Gene
journal, February 2003


Development of Additional Selectable Markers for the Halophilic Archaeon Haloferax volcanii Based on the leuB and trpA Genes
journal, February 2004


Extracellular vesicles from symbiotic vaginal lactobacilli inhibit HIV-1 infection of human tissues
journal, December 2019

  • Ñahui Palomino, Rogers A.; Vanpouille, Christophe; Laghi, Luca
  • Nature Communications, Vol. 10, Issue 1
  • DOI: 10.1038/s41467-019-13468-9

Genetic and physical mapping of DNA replication origins in Haloferax volcanii
journal, January 2005


Works referencing / citing this record:

Biocatalytic Preparation of Chiral Sulfoxides through Asymmetric Reductive Resolution by Methionine Sulfoxide Reductase A
journal, May 2018


Composite genome sequence of Bacillus clausii, a probiotic commercially available as Enterogermina®, and insights into its probiotic properties
journal, December 2019


The Functions of the Mammalian Methionine Sulfoxide Reductase System and Related Diseases
journal, September 2018