Papain-like protease 1 from transmissible gastroenteritis virus: crystal structure and enzymatic activity toward viral and cellular substrates.
Identifieur interne : 002483 ( Main/Exploration ); précédent : 002482; suivant : 002484Papain-like protease 1 from transmissible gastroenteritis virus: crystal structure and enzymatic activity toward viral and cellular substrates.
Auteurs : Justyna A. Wojdyla [Allemagne] ; Ioannis Manolaridis ; Puck B. Van Kasteren ; Marjolein Kikkert ; Eric J. Snijder ; Alexander E. Gorbalenya ; Paul A. TuckerSource :
- Journal of virology [ 1098-5514 ] ; 2010.
Descripteurs français
- KwdFr :
- Animaux, Conformation des protéines, Coronavirus (enzymologie), Coronavirus (génétique), Cristallographie aux rayons X, Données de séquences moléculaires, Humains, Interactions hôte-pathogène, Modèles moléculaires, Papaïne (), Papaïne (génétique), Papaïne (métabolisme), Protéines virales (), Protéines virales (génétique), Protéines virales (métabolisme), Protéines virales non structurales (), Protéines virales non structurales (génétique), Similitude de séquences d'acides aminés, Spécificité du substrat, Séquence d'acides aminés, Virus de la gastroentérite transmissible (enzymologie), Virus de la gastroentérite transmissible (génétique), Électricité statique.
- MESH :
- enzymologie : Coronavirus, Virus de la gastroentérite transmissible.
- génétique : Coronavirus, Papaïne, Protéines virales, Protéines virales non structurales, Virus de la gastroentérite transmissible.
- métabolisme : Papaïne, Protéines virales.
- Animaux, Conformation des protéines, Cristallographie aux rayons X, Données de séquences moléculaires, Humains, Interactions hôte-pathogène, Modèles moléculaires, Papaïne, Protéines virales, Protéines virales non structurales, Similitude de séquences d'acides aminés, Spécificité du substrat, Séquence d'acides aminés, Électricité statique.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Coronavirus (enzymology), Coronavirus (genetics), Crystallography, X-Ray, Host-Pathogen Interactions, Humans, Models, Molecular, Molecular Sequence Data, Papain (chemistry), Papain (genetics), Papain (metabolism), Protein Conformation, Sequence Homology, Amino Acid, Static Electricity, Substrate Specificity, Transmissible gastroenteritis virus (enzymology), Transmissible gastroenteritis virus (genetics), Viral Nonstructural Proteins (chemistry), Viral Nonstructural Proteins (genetics), Viral Proteins (chemistry), Viral Proteins (genetics), Viral Proteins (metabolism).
- MESH :
- chemical , chemistry : Papain, Viral Nonstructural Proteins, Viral Proteins.
- enzymology : Coronavirus, Transmissible gastroenteritis virus.
- genetics : Coronavirus, Papain, Transmissible gastroenteritis virus, Viral Nonstructural Proteins, Viral Proteins.
- chemical , metabolism : Papain, Viral Proteins.
- Amino Acid Sequence, Animals, Crystallography, X-Ray, Host-Pathogen Interactions, Humans, Models, Molecular, Molecular Sequence Data, Protein Conformation, Sequence Homology, Amino Acid, Static Electricity, Substrate Specificity.
Abstract
Coronaviruses encode two classes of cysteine proteases, which have narrow substrate specificities and either a chymotrypsin- or papain-like fold. These enzymes mediate the processing of the two precursor polyproteins of the viral replicase and are also thought to modulate host cell functions to facilitate infection. The papain-like protease 1 (PL1(pro)) domain is present in nonstructural protein 3 (nsp3) of alphacoronaviruses and subgroup 2a betacoronaviruses. It participates in the proteolytic processing of the N-terminal region of the replicase polyproteins in a manner that varies among different coronaviruses and remains poorly understood. Here we report the first structural and biochemical characterization of a purified coronavirus PL1(pro) domain, that of transmissible gastroenteritis virus (TGEV). Its tertiary structure is compared with that of severe acute respiratory syndrome (SARS) coronavirus PL2(pro), a downstream paralog that is conserved in the nsp3's of all coronaviruses. We identify both conserved and unique structural features likely controlling the interaction of PL1(pro) with cofactors and substrates, including the tentative mapping of substrate pocket residues. The purified recombinant TGEV PL1(pro) was shown to cleave a peptide mimicking the cognate nsp2|nsp3 cleavage site. Like its PL2(pro) paralogs from several coronaviruses, TGEV PL1(pro) was also found to have deubiquitinating activity in an in vitro cleavage assay, implicating it in counteracting ubiquitin-regulated host cell pathways, likely including innate immune responses. In combination with the prior characterization of PL2(pro) from other alphacoronaviruses, e.g., human coronaviruses 229E and NL63, our results unequivocally establish that these viruses employ two PL(pro)s with overlapping specificities toward both viral and cellular substrates.
DOI: 10.1128/JVI.00898-10
PubMed: 20668092
Affiliations:
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Le document en format XML
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Wojdyla</name><affiliation wicri:level="1"><nlm:affiliation>EMBL Hamburg Outstation, c/o DESY, Notkestrasse 85, D-22603 Hamburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>EMBL Hamburg Outstation, c/o DESY, Notkestrasse 85, D-22603 Hamburg</wicri:regionArea><wicri:noRegion>22603 Hamburg</wicri:noRegion><wicri:noRegion>22603 Hamburg</wicri:noRegion><wicri:noRegion>D-22603 Hamburg</wicri:noRegion></affiliation></author><author><name sortKey="Manolaridis, Ioannis" sort="Manolaridis, Ioannis" uniqKey="Manolaridis I" first="Ioannis" last="Manolaridis">Ioannis Manolaridis</name></author><author><name sortKey="Van Kasteren, Puck B" sort="Van Kasteren, Puck B" uniqKey="Van Kasteren P" first="Puck B" last="Van Kasteren">Puck B. Van Kasteren</name></author><author><name sortKey="Kikkert, Marjolein" sort="Kikkert, Marjolein" uniqKey="Kikkert M" first="Marjolein" last="Kikkert">Marjolein Kikkert</name></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J" last="Snijder">Eric J. Snijder</name></author><author><name sortKey="Gorbalenya, Alexander E" sort="Gorbalenya, Alexander E" uniqKey="Gorbalenya A" first="Alexander E" last="Gorbalenya">Alexander E. Gorbalenya</name></author><author><name sortKey="Tucker, Paul A" sort="Tucker, Paul A" uniqKey="Tucker P" first="Paul A" last="Tucker">Paul A. Tucker</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Coronavirus (enzymology)</term><term>Coronavirus (genetics)</term><term>Crystallography, X-Ray</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Papain (chemistry)</term><term>Papain (genetics)</term><term>Papain (metabolism)</term><term>Protein Conformation</term><term>Sequence Homology, Amino Acid</term><term>Static Electricity</term><term>Substrate Specificity</term><term>Transmissible gastroenteritis virus (enzymology)</term><term>Transmissible gastroenteritis virus (genetics)</term><term>Viral Nonstructural Proteins (chemistry)</term><term>Viral Nonstructural Proteins (genetics)</term><term>Viral Proteins (chemistry)</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Conformation des protéines</term><term>Coronavirus (enzymologie)</term><term>Coronavirus (génétique)</term><term>Cristallographie aux rayons X</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Modèles moléculaires</term><term>Papaïne ()</term><term>Papaïne (génétique)</term><term>Papaïne (métabolisme)</term><term>Protéines virales ()</term><term>Protéines virales (génétique)</term><term>Protéines virales (métabolisme)</term><term>Protéines virales non structurales ()</term><term>Protéines virales non structurales (génétique)</term><term>Similitude de séquences d'acides aminés</term><term>Spécificité du substrat</term><term>Séquence d'acides aminés</term><term>Virus de la gastroentérite transmissible (enzymologie)</term><term>Virus de la gastroentérite transmissible (génétique)</term><term>Électricité statique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Papain</term><term>Viral Nonstructural Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Coronavirus</term><term>Virus de la gastroentérite transmissible</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Coronavirus</term><term>Transmissible gastroenteritis virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronavirus</term><term>Papain</term><term>Transmissible gastroenteritis virus</term><term>Viral Nonstructural Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus</term><term>Papaïne</term><term>Protéines virales</term><term>Protéines virales non structurales</term><term>Virus de la gastroentérite transmissible</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Papain</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Papaïne</term><term>Protéines virales</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Crystallography, X-Ray</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Protein Conformation</term><term>Sequence Homology, Amino Acid</term><term>Static Electricity</term><term>Substrate Specificity</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Conformation des protéines</term><term>Cristallographie aux rayons X</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Modèles moléculaires</term><term>Papaïne</term><term>Protéines virales</term><term>Protéines virales non structurales</term><term>Similitude de séquences d'acides aminés</term><term>Spécificité du substrat</term><term>Séquence d'acides aminés</term><term>Électricité statique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Coronaviruses encode two classes of cysteine proteases, which have narrow substrate specificities and either a chymotrypsin- or papain-like fold. These enzymes mediate the processing of the two precursor polyproteins of the viral replicase and are also thought to modulate host cell functions to facilitate infection. The papain-like protease 1 (PL1(pro)) domain is present in nonstructural protein 3 (nsp3) of alphacoronaviruses and subgroup 2a betacoronaviruses. It participates in the proteolytic processing of the N-terminal region of the replicase polyproteins in a manner that varies among different coronaviruses and remains poorly understood. Here we report the first structural and biochemical characterization of a purified coronavirus PL1(pro) domain, that of transmissible gastroenteritis virus (TGEV). Its tertiary structure is compared with that of severe acute respiratory syndrome (SARS) coronavirus PL2(pro), a downstream paralog that is conserved in the nsp3's of all coronaviruses. We identify both conserved and unique structural features likely controlling the interaction of PL1(pro) with cofactors and substrates, including the tentative mapping of substrate pocket residues. The purified recombinant TGEV PL1(pro) was shown to cleave a peptide mimicking the cognate nsp2|nsp3 cleavage site. Like its PL2(pro) paralogs from several coronaviruses, TGEV PL1(pro) was also found to have deubiquitinating activity in an in vitro cleavage assay, implicating it in counteracting ubiquitin-regulated host cell pathways, likely including innate immune responses. In combination with the prior characterization of PL2(pro) from other alphacoronaviruses, e.g., human coronaviruses 229E and NL63, our results unequivocally establish that these viruses employ two PL(pro)s with overlapping specificities toward both viral and cellular substrates.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country></list><tree><noCountry><name sortKey="Gorbalenya, Alexander E" sort="Gorbalenya, Alexander E" uniqKey="Gorbalenya A" first="Alexander E" last="Gorbalenya">Alexander E. Gorbalenya</name><name sortKey="Kikkert, Marjolein" sort="Kikkert, Marjolein" uniqKey="Kikkert M" first="Marjolein" last="Kikkert">Marjolein Kikkert</name><name sortKey="Manolaridis, Ioannis" sort="Manolaridis, Ioannis" uniqKey="Manolaridis I" first="Ioannis" last="Manolaridis">Ioannis Manolaridis</name><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J" last="Snijder">Eric J. Snijder</name><name sortKey="Tucker, Paul A" sort="Tucker, Paul A" uniqKey="Tucker P" first="Paul A" last="Tucker">Paul A. Tucker</name><name sortKey="Van Kasteren, Puck B" sort="Van Kasteren, Puck B" uniqKey="Van Kasteren P" first="Puck B" last="Van Kasteren">Puck B. Van Kasteren</name></noCountry><country name="Allemagne"><noRegion><name sortKey="Wojdyla, Justyna A" sort="Wojdyla, Justyna A" uniqKey="Wojdyla J" first="Justyna A" last="Wojdyla">Justyna A. Wojdyla</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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