Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease.
Identifieur interne : 000F53 ( Main/Exploration ); précédent : 000F52; suivant : 000F54Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease.
Auteurs : Mikl S Békés [États-Unis] ; Gerbrand J. Van Der Heden Van Noort [Pays-Bas] ; Reggy Ekkebus [Pays-Bas] ; Huib Ovaa [Pays-Bas] ; Tony T. Huang [États-Unis] ; Christopher D. Lima [États-Unis]Source :
- Molecular cell [ 1097-4164 ] ; 2016.
Descripteurs français
- KwdFr :
- Cellules HeLa, Conformation des protéines, Cysteine endopeptidases (), Cysteine endopeptidases (génétique), Cysteine endopeptidases (métabolisme), Cytokines (), Cytokines (métabolisme), Enzymes de désubiquitinylation (), Enzymes de désubiquitinylation (métabolisme), Humains, Liaison aux protéines, Lysine, Modèles moléculaires, Motifs et domaines d'intéraction protéique, Mutation, Polyubiquitine (), Polyubiquitine (métabolisme), Protéines virales (), Protéines virales (génétique), Protéines virales (métabolisme), Relation structure-activité, Sites de fixation, Ubiquitines (), Ubiquitines (métabolisme), Ubiquitinylation, Virus du SRAS (enzymologie), Virus du SRAS (génétique).
- MESH :
- enzymologie : Virus du SRAS.
- génétique : Cysteine endopeptidases, Protéines virales, Virus du SRAS.
- métabolisme : Cysteine endopeptidases, Cytokines, Enzymes de désubiquitinylation, Polyubiquitine, Protéines virales, Ubiquitines.
- Cellules HeLa, Conformation des protéines, Cysteine endopeptidases, Cytokines, Enzymes de désubiquitinylation, Humains, Liaison aux protéines, Lysine, Modèles moléculaires, Motifs et domaines d'intéraction protéique, Mutation, Polyubiquitine, Protéines virales, Relation structure-activité, Sites de fixation, Ubiquitines, Ubiquitinylation.
English descriptors
- KwdEn :
- Binding Sites, Cysteine Endopeptidases (chemistry), Cysteine Endopeptidases (genetics), Cysteine Endopeptidases (metabolism), Cytokines (chemistry), Cytokines (metabolism), Deubiquitinating Enzymes (chemistry), Deubiquitinating Enzymes (metabolism), HeLa Cells, Humans, Lysine, Models, Molecular, Mutation, Polyubiquitin (chemistry), Polyubiquitin (metabolism), Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, SARS Virus (enzymology), SARS Virus (genetics), Structure-Activity Relationship, Ubiquitination, Ubiquitins (chemistry), Ubiquitins (metabolism), Viral Proteins (chemistry), Viral Proteins (genetics), Viral Proteins (metabolism).
- MESH :
- chemical , chemistry : Cysteine Endopeptidases, Cytokines, Deubiquitinating Enzymes, Polyubiquitin, Ubiquitins, Viral Proteins.
- chemical , genetics : Cysteine Endopeptidases, Viral Proteins.
- chemical , metabolism : Cysteine Endopeptidases, Cytokines, Deubiquitinating Enzymes, Polyubiquitin, Ubiquitins, Viral Proteins.
- enzymology : SARS Virus.
- genetics : SARS Virus.
- Binding Sites, HeLa Cells, Humans, Lysine, Models, Molecular, Mutation, Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, Structure-Activity Relationship, Ubiquitination.
Abstract
Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific polyubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The severe acute respiratory syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two-domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1-S1' preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections.
DOI: 10.1016/j.molcel.2016.04.016
PubMed: 27203180
Affiliations:
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Electronic address: limac@mskcc.org.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Structural Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA; Howard Hughes Medical Institute, 1275 York Avenue, New York, NY 10065</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><series><title level="j">Molecular cell</title><idno type="eISSN">1097-4164</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Binding Sites</term><term>Cysteine Endopeptidases (chemistry)</term><term>Cysteine Endopeptidases (genetics)</term><term>Cysteine Endopeptidases (metabolism)</term><term>Cytokines (chemistry)</term><term>Cytokines (metabolism)</term><term>Deubiquitinating Enzymes (chemistry)</term><term>Deubiquitinating Enzymes (metabolism)</term><term>HeLa Cells</term><term>Humans</term><term>Lysine</term><term>Models, Molecular</term><term>Mutation</term><term>Polyubiquitin (chemistry)</term><term>Polyubiquitin (metabolism)</term><term>Protein Binding</term><term>Protein Conformation</term><term>Protein Interaction Domains and Motifs</term><term>SARS Virus (enzymology)</term><term>SARS Virus (genetics)</term><term>Structure-Activity Relationship</term><term>Ubiquitination</term><term>Ubiquitins (chemistry)</term><term>Ubiquitins (metabolism)</term><term>Viral Proteins (chemistry)</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cellules HeLa</term><term>Conformation des protéines</term><term>Cysteine endopeptidases ()</term><term>Cysteine endopeptidases (génétique)</term><term>Cysteine endopeptidases (métabolisme)</term><term>Cytokines ()</term><term>Cytokines (métabolisme)</term><term>Enzymes de désubiquitinylation ()</term><term>Enzymes de désubiquitinylation (métabolisme)</term><term>Humains</term><term>Liaison aux protéines</term><term>Lysine</term><term>Modèles moléculaires</term><term>Motifs et domaines d'intéraction protéique</term><term>Mutation</term><term>Polyubiquitine ()</term><term>Polyubiquitine (métabolisme)</term><term>Protéines virales ()</term><term>Protéines virales (génétique)</term><term>Protéines virales (métabolisme)</term><term>Relation structure-activité</term><term>Sites de fixation</term><term>Ubiquitines ()</term><term>Ubiquitines (métabolisme)</term><term>Ubiquitinylation</term><term>Virus du SRAS (enzymologie)</term><term>Virus du SRAS (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Cytokines</term><term>Deubiquitinating Enzymes</term><term>Polyubiquitin</term><term>Ubiquitins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Cytokines</term><term>Deubiquitinating Enzymes</term><term>Polyubiquitin</term><term>Ubiquitins</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="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Protéines virales</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Cytokines</term><term>Enzymes de désubiquitinylation</term><term>Polyubiquitine</term><term>Protéines virales</term><term>Ubiquitines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term><term>HeLa Cells</term><term>Humans</term><term>Lysine</term><term>Models, Molecular</term><term>Mutation</term><term>Protein Binding</term><term>Protein Conformation</term><term>Protein Interaction Domains and Motifs</term><term>Structure-Activity Relationship</term><term>Ubiquitination</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules HeLa</term><term>Conformation des protéines</term><term>Cysteine endopeptidases</term><term>Cytokines</term><term>Enzymes de désubiquitinylation</term><term>Humains</term><term>Liaison aux protéines</term><term>Lysine</term><term>Modèles moléculaires</term><term>Motifs et domaines d'intéraction protéique</term><term>Mutation</term><term>Polyubiquitine</term><term>Protéines virales</term><term>Relation structure-activité</term><term>Sites de fixation</term><term>Ubiquitines</term><term>Ubiquitinylation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific polyubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The severe acute respiratory syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two-domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1-S1' preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li><li>États-Unis</li></country><region><li>État de New York</li></region></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="Pays-Bas"><noRegion><name sortKey="Van Der Heden Van Noort, Gerbrand J" sort="Van Der Heden Van Noort, Gerbrand J" uniqKey="Van Der Heden Van Noort G" first="Gerbrand J" last="Van Der Heden Van Noort">Gerbrand J. Van Der Heden Van Noort</name></noRegion><name sortKey="Ekkebus, Reggy" sort="Ekkebus, Reggy" uniqKey="Ekkebus R" first="Reggy" last="Ekkebus">Reggy Ekkebus</name><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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