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Title: Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication and antagonize the host innate immune response. The latter function involves reversing the post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon-stimulated gene product 15 (ISG15). Ub is known to be highly conserved among eukaryotes, but surprisingly, ISG15 is highly divergent among animals. The ramifications of this sequence divergence to the recognition of ISG15 by coronavirus PLPs at a structural and biochemical level are poorly understood. Therefore, the activity of PLPs from SARS-CoV, MERS–CoV, and mouse hepatitis virus was evaluated against seven ISG15s originating from an assortment of animal species susceptible, and not, to certain coronavirus infections. Excitingly, our kinetic, thermodynamic, and structural analysis revealed an array of different preferences among PLPs. Included in these studies is the first insight into a coronavirus PLP’s interface with ISG15 via SARS-CoV PLpro in complex with the principle binding domain of human ISG15 (hISG15) and mouse ISG15s (mISG15s). Here, the first X-ray structure of the full-length mISG15 protein is also reported and highlights a unique, twisted hinge regionmore » of ISG15 that is not conserved in hISG15, suggesting a potential role in differential recognition. Taken together, this new information provides a structural and biochemical understanding of the distinct specificities among coronavirus PLPs observed and addresses a critical gap of how PLPs can interact with ISG15s from a wide variety of species.« less

Authors:
 [1];  [1];  [2];  [1];  [2];  [1]
+ Show Author Affiliations
  1. Univ. of Georgia, Athens, GA (United States)
  2. Purdue Univ., West Lafayette, IN (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); NIH/NIAID
OSTI Identifier:
1368288
Alternate Identifier(s):
OSTI ID: 1415315
Grant/Contract Number:  
W-31-109-Eng-38; 1R01AI109008; R01AI085089
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Molecular Biology
Additional Journal Information:
Journal Volume: 429; Journal Issue: 11; Journal ID: ISSN 0022-2836
Publisher:
Elsevier
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; ISG15; ubiquitin; coronavirus; Middle East respiratory syndrome; severe acute respiratory syndrome

Citation Formats

Daczkowski, Courtney M., Dzimianski, John V., Clasman, Jozlyn R., Goodwin, Octavia, Mesecar, Andrew D., and Pegan, Scott D. Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species. United States: N. p., 2017. Web. doi:10.1016/j.jmb.2017.04.011.
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Daczkowski, Courtney M., Dzimianski, John V., Clasman, Jozlyn R., Goodwin, Octavia, Mesecar, Andrew D., & Pegan, Scott D. Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species. United States. https://doi.org/10.1016/j.jmb.2017.04.011
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Daczkowski, Courtney M., Dzimianski, John V., Clasman, Jozlyn R., Goodwin, Octavia, Mesecar, Andrew D., and Pegan, Scott D. Fri . "Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species". United States. https://doi.org/10.1016/j.jmb.2017.04.011. https://www.osti.gov/servlets/purl/1368288.
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@article{osti_1368288,
title = {Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species},
author = {Daczkowski, Courtney M. and Dzimianski, John V. and Clasman, Jozlyn R. and Goodwin, Octavia and Mesecar, Andrew D. and Pegan, Scott D.},
abstractNote = {Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication and antagonize the host innate immune response. The latter function involves reversing the post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon-stimulated gene product 15 (ISG15). Ub is known to be highly conserved among eukaryotes, but surprisingly, ISG15 is highly divergent among animals. The ramifications of this sequence divergence to the recognition of ISG15 by coronavirus PLPs at a structural and biochemical level are poorly understood. Therefore, the activity of PLPs from SARS-CoV, MERS–CoV, and mouse hepatitis virus was evaluated against seven ISG15s originating from an assortment of animal species susceptible, and not, to certain coronavirus infections. Excitingly, our kinetic, thermodynamic, and structural analysis revealed an array of different preferences among PLPs. Included in these studies is the first insight into a coronavirus PLP’s interface with ISG15 via SARS-CoV PLpro in complex with the principle binding domain of human ISG15 (hISG15) and mouse ISG15s (mISG15s). Here, the first X-ray structure of the full-length mISG15 protein is also reported and highlights a unique, twisted hinge region of ISG15 that is not conserved in hISG15, suggesting a potential role in differential recognition. Taken together, this new information provides a structural and biochemical understanding of the distinct specificities among coronavirus PLPs observed and addresses a critical gap of how PLPs can interact with ISG15s from a wide variety of species.},
doi = {10.1016/j.jmb.2017.04.011},
journal = {Journal of Molecular Biology},
number = 11,
volume = 429,
place = {United States},
year = {Fri Apr 21 00:00:00 EDT 2017},
month = {Fri Apr 21 00:00:00 EDT 2017}
}
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https://doi.org/10.1016/j.jmb.2017.04.011
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Works referenced in this record:

Coronaviruses post-SARS: update on replication and pathogenesis
journal, May 2009

  • Perlman, Stanley; Netland, Jason
  • Nature Reviews Microbiology, Vol. 7, Issue 6
  • DOI: 10.1038/nrmicro2147

From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses
journal, October 2013

Mechanisms and enzymes involved in SARS coronavirus genome expression
journal, September 2003

  • Thiel, Volker; Ivanov, Konstantin A.; Putics, Ákos
  • Journal of General Virology, Vol. 84, Issue 9
  • DOI: 10.1099/vir.0.19424-0

The Papain-Like Protease of Severe Acute Respiratory Syndrome Coronavirus Has Deubiquitinating Activity
journal, November 2005

Severe acute respiratory syndrome coronavirus papain-like protease: Structure of a viral deubiquitinating enzyme
journal, March 2006

  • Ratia, K.; Saikatendu, K. S.; Santarsiero, B. D.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 15
  • DOI: 10.1073/pnas.0510851103

Identification of Severe Acute Respiratory Syndrome Coronavirus Replicase Products and Characterization of Papain-Like Protease Activity
journal, December 2004

Murine Coronavirus Ubiquitin-Like Domain Is Important for Papain-Like Protease Stability and Viral Pathogenesis
journal, February 2015

  • Mielech, Anna M.; Deng, Xufang; Chen, Yafang
  • Journal of Virology, Vol. 89, Issue 9
  • DOI: 10.1128/JVI.00338-15

Selectivity in ISG15 and ubiquitin recognition by the SARS coronavirus papain-like protease
journal, October 2007

  • Lindner, Holger A.; Lytvyn, Viktoria; Qi, Hongtao
  • Archives of Biochemistry and Biophysics, Vol. 466, Issue 1
  • DOI: 10.1016/j.abb.2007.07.006

Regulation of IRF-3-dependent Innate Immunity by the Papain-like Protease Domain of the Severe Acute Respiratory Syndrome Coronavirus
journal, August 2007

  • Devaraj, Santhana G.; Wang, Nan; Chen, Zhongbin
  • Journal of Biological Chemistry, Vol. 282, Issue 44
  • DOI: 10.1074/jbc.M704870200

Severe Acute Respiratory Syndrome Coronavirus Papain-Like Protease Ubiquitin-Like Domain and Catalytic Domain Regulate Antagonism of IRF3 and NF-κB Signaling
journal, April 2009

  • Frieman, Matthew; Ratia, Kiira; Johnston, Robert E.
  • Journal of Virology, Vol. 83, Issue 13
  • DOI: 10.1128/JVI.02220-08

Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating Activity of SARS-CoV Papain-Like Protease
journal, May 2014

Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease
journal, May 2016

  • Békés, Miklós; van der Heden van Noort, Gerbrand J.; Ekkebus, Reggy
  • Molecular Cell, Vol. 62, Issue 4
  • DOI: 10.1016/j.molcel.2016.04.016

Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia
journal, November 2012

  • Zaki, Ali M.; van Boheemen, Sander; Bestebroer, Theo M.
  • New England Journal of Medicine, Vol. 367, Issue 19
  • DOI: 10.1056/NEJMoa1211721

Discovery of Novel Alphacoronaviruses in European Rodents and Shrews
journal, March 2016

  • Tsoleridis, Theocharis; Onianwa, Okechukwu; Horncastle, Emma
  • Viruses, Vol. 8, Issue 3
  • DOI: 10.3390/v8030084

Species Specificity of the NS1 Protein of Influenza B Virus: NS1 BINDS ONLY HUMAN AND NON-HUMAN PRIMATE UBIQUITIN-LIKE ISG15 PROTEINS
journal, January 2010

  • Sridharan, Haripriya; Zhao, Chen; Krug, Robert M.
  • Journal of Biological Chemistry, Vol. 285, Issue 11
  • DOI: 10.1074/jbc.C109.095703

Mice Lacking the ISG15 E1 Enzyme UbE1L Demonstrate Increased Susceptibility to both Mouse-Adapted and Non-Mouse-Adapted Influenza B Virus Infection
journal, November 2008

  • Lai, Caroline; Struckhoff, Jessica J.; Schneider, Jana
  • Journal of Virology, Vol. 83, Issue 2
  • DOI: 10.1128/JVI.00105-08

Viral tricks to grid-lock the type I interferon system
journal, August 2010

Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species
journal, July 2016

  • Deaton, M. K.; Dzimianski, J. V.; Daczkowski, C. M.
  • Journal of Virology, Vol. 90, Issue 18
  • DOI: 10.1128/JVI.00975-16

Catalytic Function and Substrate Specificity of the Papain-Like Protease Domain of nsp3 from the Middle East Respiratory Syndrome Coronavirus
journal, August 2014

  • Baez-Santos, Y. M.; Mielech, A. M.; Deng, X.
  • Journal of Virology, Vol. 88, Issue 21
  • DOI: 10.1128/JVI.01294-14

A Chimeric Virus-Mouse Model System for Evaluating the Function and Inhibition of Papain-Like Proteases of Emerging Coronaviruses
journal, August 2014

  • Deng, X.; Agnihothram, S.; Mielech, A. M.
  • Journal of Virology, Vol. 88, Issue 20
  • DOI: 10.1128/JVI.01749-14

Structural basis for the removal of ubiquitin and interferon-stimulated gene 15 by a viral ovarian tumor domain-containing protease
journal, January 2011

  • James, T. W.; Frias-Staheli, N.; Bacik, J. -P.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 6
  • DOI: 10.1073/pnas.1013388108

Molecular basis for ubiquitin and ISG15 cross-reactivity in viral ovarian tumor domains
journal, January 2011

  • Akutsu, M.; Ye, Y.; Virdee, S.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 6
  • DOI: 10.1073/pnas.1015287108

Crystal Structure of the Interferon-induced Ubiquitin-like Protein ISG15
journal, May 2005

  • Narasimhan, Jana; Wang, Ming; Fu, Zhuji
  • Journal of Biological Chemistry, Vol. 280, Issue 29
  • DOI: 10.1074/jbc.M502814200

Structural basis for the sequence-specific recognition of human ISG15 by the NS1 protein of influenza B virus
journal, August 2011

  • Guan, R.; Ma, L. -C.; Leonard, P. G.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 33
  • DOI: 10.1073/pnas.1107032108

The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN- / -induced ubiquitin-like protein
journal, May 2004

  • Zhao, C.; Beaudenon, S. L.; Kelley, M. L.
  • Proceedings of the National Academy of Sciences, Vol. 101, Issue 20
  • DOI: 10.1073/pnas.0402528101

ISG15 deficiency and increased viral resistance in humans but not mice
journal, May 2016

  • Speer, Scott D.; Li, Zhi; Buta, Sofija
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms11496

X-ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-like Proteases
journal, March 2014

  • Báez-Santos, Yahira M.; Barraza, Scott J.; Wilson, Michael W.
  • Journal of Medicinal Chemistry, Vol. 57, Issue 6
  • DOI: 10.1021/jm401712t

Evidence of Kinetic Cooperativity in Dimeric Ketopantoate Reductase from Staphylococcus aureus
journal, May 2015

[20] Processing of X-ray diffraction data collected in oscillation mode
book, January 1997

Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206

Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard
journal, December 2007

  • Terwilliger, Thomas C.; Grosse-Kunstleve, Ralf W.; Afonine, Pavel V.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 64, Issue 1
  • DOI: 10.1107/S090744490705024X

Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

  • Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
  • DOI: 10.1107/S0907444909042073

PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations
journal, July 2004

  • Dolinsky, T. J.; Nielsen, J. E.; McCammon, J. A.
  • Nucleic Acids Research, Vol. 32, Issue Web Server, p. W665-W667
  • DOI: 10.1093/nar/gkh381

Selectivity in ISG15 and ubiquitin recognition by the SARS coronavirus papain-like protease
journal, October 2007

  • Lindner, Holger A.; Lytvyn, Viktoria; Qi, Hongtao
  • Archives of Biochemistry and Biophysics, Vol. 466, Issue 1
  • DOI: 10.1016/j.abb.2007.07.006

From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses
journal, October 2013

Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease
journal, May 2016

  • Békés, Miklós; van der Heden van Noort, Gerbrand J.; Ekkebus, Reggy
  • Molecular Cell, Vol. 62, Issue 4
  • DOI: 10.1016/j.molcel.2016.04.016

X-ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-like Proteases
journal, March 2014

  • Báez-Santos, Yahira M.; Barraza, Scott J.; Wilson, Michael W.
  • Journal of Medicinal Chemistry, Vol. 57, Issue 6
  • DOI: 10.1021/jm401712t

ISG15 deficiency and increased viral resistance in humans but not mice
journal, May 2016

  • Speer, Scott D.; Li, Zhi; Buta, Sofija
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms11496

Coronaviruses post-SARS: update on replication and pathogenesis
journal, May 2009

  • Perlman, Stanley; Netland, Jason
  • Nature Reviews Microbiology, Vol. 7, Issue 6
  • DOI: 10.1038/nrmicro2147

Emerging Human Coronaviruses — Disease Potential and Preparedness
journal, November 2012

  • Anderson, Larry J.; Baric, Ralph S.
  • New England Journal of Medicine, Vol. 367, Issue 19
  • DOI: 10.1056/nejme1212300

Structural basis for the removal of ubiquitin and interferon-stimulated gene 15 by a viral ovarian tumor domain-containing protease
journal, January 2011

  • James, T. W.; Frias-Staheli, N.; Bacik, J. -P.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 6
  • DOI: 10.1073/pnas.1013388108

Molecular basis for ubiquitin and ISG15 cross-reactivity in viral ovarian tumor domains
journal, January 2011

  • Akutsu, M.; Ye, Y.; Virdee, S.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 6
  • DOI: 10.1073/pnas.1015287108

PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations
journal, July 2004

  • Dolinsky, T. J.; Nielsen, J. E.; McCammon, J. A.
  • Nucleic Acids Research, Vol. 32, Issue Web Server, p. W665-W667
  • DOI: 10.1093/nar/gkh381

PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.45787

Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard.
journalarticle, January 2008

  • Terwilliger, Thomas C.; Grosse-Kunstleve, Ralf W.; Afonine, Pavel V.
  • International Union of Crystallography (IUCr)
  • DOI: 10.17863/cam.52329

Discovery of Novel Alphacoronaviruses in European Rodents and Shrews
journal, March 2016

  • Tsoleridis, Theocharis; Onianwa, Okechukwu; Horncastle, Emma
  • Viruses, Vol. 8, Issue 3
  • DOI: 10.3390/v8030084
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    Works referencing / citing this record:

    The papain-like protease determines a virulence trait that varies among members of the SARS-coronavirus species
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    Determining the molecular drivers of species-specific interferon-stimulated gene product 15 interactions with nairovirus ovarian tumor domain proteases
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    Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity
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    ISG15 in antiviral immunity and beyond
    journal, May 2018

    Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement
    journal, January 2019

    • Langley, Caroline; Goodwin, Octavia; Dzimianski, John V.
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    ISGylation – a key to lock the cell gates for preventing the spread of threats
    journal, August 2017

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    USP18 – a multifunctional component in the interferon response
    journal, November 2018

    • Basters, Anja; Knobeloch, Klaus-Peter; Fritz, Günter
    • Bioscience Reports, Vol. 38, Issue 6
    • DOI: 10.1042/bsr20180250

    The papain-like protease determines a virulence trait that varies among members of the SARS-coronavirus species.
    text, January 2018

    • Niemeyer, Daniela; Mösbauer, Kirstin; Klein, Eva M.
    • Public Library of Science
    • DOI: 10.7892/boris.127515

    Decoupling deISGylating and deubiquitinating activities of the MERS virus papain-like protease
    journal, February 2020

    ISG15: It's Complicated
    journal, October 2019

    • Dzimianski, John V.; Scholte, Florine E. M.; Bergeron, Éric
    • Journal of Molecular Biology, Vol. 431, Issue 21
    • DOI: 10.1016/j.jmb.2019.03.013

    ISG15 in antiviral immunity and beyond
    journal, May 2018

    The current landscape of coronavirus-host protein–protein interactions
    journal, August 2020

    • Perrin-Cocon, Laure; Diaz, Olivier; Jacquemin, Clémence
    • Journal of Translational Medicine, Vol. 18, Issue 1
    • DOI: 10.1186/s12967-020-02480-z

    Determining the molecular drivers of species-specific interferon-stimulated gene product 15 interactions with nairovirus ovarian tumor domain proteases
    journal, December 2019

    The papain-like protease determines a virulence trait that varies among members of the SARS-coronavirus species
    journal, September 2018

    Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity
    journal, January 2019

    COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms
    journal, March 2021

    • Malone, Robert W.; Tisdall, Philip; Fremont-Smith, Philip
    • Frontiers in Pharmacology, Vol. 12
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    • Clemente, Valentino; D’Arcy, Padraig; Bazzaro, Martina
    • International Journal of Molecular Sciences, Vol. 21, Issue 10
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