SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme.
Identifieur interne : 001584 ( Main/Exploration ); précédent : 001583; suivant : 001585SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme.
Auteurs : Mikl S Békés [États-Unis] ; Wioletta Rut [Pologne] ; Paulina Kasperkiewicz [Pologne] ; Monique P C. Mulder [Pays-Bas] ; Huib Ovaa [Pays-Bas] ; Marcin Drag [Pologne] ; Christopher D. Lima [États-Unis] ; Tony T. Huang [États-Unis]Source :
- The Biochemical journal [ 1470-8728 ] ; 2015.
Descripteurs français
- KwdFr :
- Conformation des protéines, Endopeptidases (métabolisme), Humains, Infections à coronavirus (métabolisme), Infections à coronavirus (virologie), Lysine (métabolisme), Maturation post-traductionnelle des protéines, Papaïne (métabolisme), Peptide hydrolases (métabolisme), Protéines virales (métabolisme), Spécificité du substrat, Ubiquitine (métabolisme), Ubiquitinylation, Virus du SRAS (enzymologie).
- MESH :
- enzymologie : Virus du SRAS.
- métabolisme : Endopeptidases, Infections à coronavirus, Lysine, Papaïne, Peptide hydrolases, Protéines virales, Ubiquitine.
- virologie : Infections à coronavirus.
- Conformation des protéines, Humains, Maturation post-traductionnelle des protéines, Spécificité du substrat, Ubiquitinylation.
English descriptors
- KwdEn :
- Coronavirus Infections (metabolism), Coronavirus Infections (virology), Endopeptidases (metabolism), Humans, Lysine (metabolism), Papain (metabolism), Peptide Hydrolases (metabolism), Protein Conformation, Protein Processing, Post-Translational, SARS Virus (enzymology), Substrate Specificity, Ubiquitin (metabolism), Ubiquitination, Viral Proteins (metabolism).
- MESH :
- chemical , metabolism : Endopeptidases, Lysine, Papain, Peptide Hydrolases, Ubiquitin, Viral Proteins.
- enzymology : SARS Virus.
- metabolism : Coronavirus Infections.
- virology : Coronavirus Infections.
- Humans, Protein Conformation, Protein Processing, Post-Translational, Substrate Specificity, Ubiquitination.
Abstract
Ubiquitin (Ub) and the Ub-like (Ubl) modifier interferon-stimulated gene 15 (ISG15) participate in the host defence of viral infections. Viruses, including the severe acute respiratory syndrome human coronavirus (SARS hCoV), have co-opted Ub-ISG15 conjugation pathways for their own advantage or have evolved effector proteins to counter pro-inflammatory properties of Ub-ISG15-conjugated host proteins. In the present study, we compare substrate specificities of the papain-like protease (PLpro) from the recently emerged Middle East respiratory syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through biochemical assays, we show that, similar to SARS PLpro, MERS PLpro is both a deubiquitinating (DUB) and a deISGylating enzyme. Further analysis of the intrinsic DUB activity of these viral proteases revealed unique differences between the recognition and cleavage specificities of polyUb chains. First, MERS PLpro shows broad linkage specificity for the cleavage of polyUb chains, whereas SARS PLpro prefers to cleave Lys48-linked polyUb chains. Secondly, MERS PLpro cleaves polyUb chains in a 'mono-distributive' manner (one Ub at a time) and SARS PLpro prefers to cleave Lys48-linked polyUb chains by sensing a di-Ub moiety as a minimal recognition element using a 'di-distributive' cleavage mechanism. The di-distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP (Ub-specific protease)-family DUBs, as related USP family members from humans do not display such a mechanism. We propose that these intrinsic enzymatic differences between SARS and MERS PLpro will help to identify pro-inflammatory substrates of these viral DUBs and can guide in the design of therapeutics to combat infection by coronaviruses.
DOI: 10.1042/BJ20141170
PubMed: 25764917
Affiliations:
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Wyspianskiego 27, Wroclaw 50-370, Poland.</nlm:affiliation><country xml:lang="fr">Pologne</country><wicri:regionArea>†Division of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wyb. Wyspianskiego 27, Wroclaw 50-370</wicri:regionArea><wicri:noRegion>Wroclaw 50-370</wicri:noRegion></affiliation></author><author><name sortKey="Kasperkiewicz, Paulina" sort="Kasperkiewicz, Paulina" uniqKey="Kasperkiewicz P" first="Paulina" last="Kasperkiewicz">Paulina Kasperkiewicz</name><affiliation wicri:level="1"><nlm:affiliation>†Division of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wyb. Wyspianskiego 27, Wroclaw 50-370, Poland.</nlm:affiliation><country xml:lang="fr">Pologne</country><wicri:regionArea>†Division of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wyb. Wyspianskiego 27, Wroclaw 50-370</wicri:regionArea><wicri:noRegion>Wroclaw 50-370</wicri:noRegion></affiliation></author><author><name sortKey="Mulder, Monique P C" sort="Mulder, Monique P C" uniqKey="Mulder M" first="Monique P C" last="Mulder">Monique P C. Mulder</name><affiliation wicri:level="3"><nlm:affiliation>‡Division of Cell Biology, Netherlands Cancer Institute (NKI), Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>‡Division of Cell Biology, Netherlands Cancer Institute (NKI), Plesmanlaan 121, 1066 CX, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Ovaa, Huib" sort="Ovaa, Huib" uniqKey="Ovaa H" first="Huib" last="Ovaa">Huib Ovaa</name><affiliation wicri:level="3"><nlm:affiliation>‡Division of Cell Biology, Netherlands Cancer Institute (NKI), Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>‡Division of Cell Biology, Netherlands Cancer Institute (NKI), Plesmanlaan 121, 1066 CX, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Drag, Marcin" sort="Drag, Marcin" uniqKey="Drag M" first="Marcin" last="Drag">Marcin Drag</name><affiliation wicri:level="1"><nlm:affiliation>†Division of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wyb. Wyspianskiego 27, Wroclaw 50-370, Poland.</nlm:affiliation><country xml:lang="fr">Pologne</country><wicri:regionArea>†Division of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wyb. Wyspianskiego 27, Wroclaw 50-370</wicri:regionArea><wicri:noRegion>Wroclaw 50-370</wicri:noRegion></affiliation></author><author><name sortKey="Lima, Christopher D" sort="Lima, Christopher D" uniqKey="Lima C" first="Christopher D" last="Lima">Christopher D. Lima</name><affiliation wicri:level="2"><nlm:affiliation>§Structural Biology Program, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, U.S.A.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>§Structural Biology Program, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Huang, Tony T" sort="Huang, Tony T" uniqKey="Huang T" first="Tony T" last="Huang">Tony T. Huang</name><affiliation wicri:level="2"><nlm:affiliation>*Department of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, U.S.A.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>*Department of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, NY 10016</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><series><title level="j">The Biochemical journal</title><idno type="eISSN">1470-8728</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus Infections (metabolism)</term><term>Coronavirus Infections (virology)</term><term>Endopeptidases (metabolism)</term><term>Humans</term><term>Lysine (metabolism)</term><term>Papain (metabolism)</term><term>Peptide Hydrolases (metabolism)</term><term>Protein Conformation</term><term>Protein Processing, Post-Translational</term><term>SARS Virus (enzymology)</term><term>Substrate Specificity</term><term>Ubiquitin (metabolism)</term><term>Ubiquitination</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Conformation des protéines</term><term>Endopeptidases (métabolisme)</term><term>Humains</term><term>Infections à coronavirus (métabolisme)</term><term>Infections à coronavirus (virologie)</term><term>Lysine (métabolisme)</term><term>Maturation post-traductionnelle des protéines</term><term>Papaïne (métabolisme)</term><term>Peptide hydrolases (métabolisme)</term><term>Protéines virales (métabolisme)</term><term>Spécificité du substrat</term><term>Ubiquitine (métabolisme)</term><term>Ubiquitinylation</term><term>Virus du SRAS (enzymologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Endopeptidases</term><term>Lysine</term><term>Papain</term><term>Peptide Hydrolases</term><term>Ubiquitin</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Endopeptidases</term><term>Infections à coronavirus</term><term>Lysine</term><term>Papaïne</term><term>Peptide hydrolases</term><term>Protéines virales</term><term>Ubiquitine</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Protein Conformation</term><term>Protein Processing, Post-Translational</term><term>Substrate Specificity</term><term>Ubiquitination</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Conformation des protéines</term><term>Humains</term><term>Maturation post-traductionnelle des protéines</term><term>Spécificité du substrat</term><term>Ubiquitinylation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Ubiquitin (Ub) and the Ub-like (Ubl) modifier interferon-stimulated gene 15 (ISG15) participate in the host defence of viral infections. Viruses, including the severe acute respiratory syndrome human coronavirus (SARS hCoV), have co-opted Ub-ISG15 conjugation pathways for their own advantage or have evolved effector proteins to counter pro-inflammatory properties of Ub-ISG15-conjugated host proteins. In the present study, we compare substrate specificities of the papain-like protease (PLpro) from the recently emerged Middle East respiratory syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through biochemical assays, we show that, similar to SARS PLpro, MERS PLpro is both a deubiquitinating (DUB) and a deISGylating enzyme. Further analysis of the intrinsic DUB activity of these viral proteases revealed unique differences between the recognition and cleavage specificities of polyUb chains. First, MERS PLpro shows broad linkage specificity for the cleavage of polyUb chains, whereas SARS PLpro prefers to cleave Lys48-linked polyUb chains. Secondly, MERS PLpro cleaves polyUb chains in a 'mono-distributive' manner (one Ub at a time) and SARS PLpro prefers to cleave Lys48-linked polyUb chains by sensing a di-Ub moiety as a minimal recognition element using a 'di-distributive' cleavage mechanism. The di-distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP (Ub-specific protease)-family DUBs, as related USP family members from humans do not display such a mechanism. We propose that these intrinsic enzymatic differences between SARS and MERS PLpro will help to identify pro-inflammatory substrates of these viral DUBs and can guide in the design of therapeutics to combat infection by coronaviruses. </div></front></TEI><affiliations><list><country><li>Pays-Bas</li><li>Pologne</li><li>États-Unis</li></country><region><li>Hollande-Septentrionale</li><li>État de New York</li></region><settlement><li>Amsterdam</li></settlement></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Bekes, Mikl S" sort="Bekes, Mikl S" uniqKey="Bekes M" first="Mikl S" last="Békés">Mikl S Békés</name></region><name sortKey="Huang, Tony T" sort="Huang, Tony T" uniqKey="Huang T" first="Tony T" last="Huang">Tony T. Huang</name><name sortKey="Lima, Christopher D" sort="Lima, Christopher D" uniqKey="Lima C" first="Christopher D" last="Lima">Christopher D. Lima</name></country><country name="Pologne"><noRegion><name sortKey="Rut, Wioletta" sort="Rut, Wioletta" uniqKey="Rut W" first="Wioletta" last="Rut">Wioletta Rut</name></noRegion><name sortKey="Drag, Marcin" sort="Drag, Marcin" uniqKey="Drag M" first="Marcin" last="Drag">Marcin Drag</name><name sortKey="Kasperkiewicz, Paulina" sort="Kasperkiewicz, Paulina" uniqKey="Kasperkiewicz P" first="Paulina" last="Kasperkiewicz">Paulina Kasperkiewicz</name></country><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Mulder, Monique P C" sort="Mulder, Monique P C" uniqKey="Mulder M" first="Monique P C" last="Mulder">Monique P C. Mulder</name></region><name sortKey="Ovaa, Huib" sort="Ovaa, Huib" uniqKey="Ovaa H" first="Huib" last="Ovaa">Huib Ovaa</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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