Crystal Structure of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Papain-like Protease Bound to Ubiquitin Facilitates Targeted Disruption of Deubiquitinating Activity to Demonstrate Its Role in Innate Immune Suppression*
Identifieur interne : 000F32 ( Ncbi/Merge ); précédent : 000F31; suivant : 000F33Crystal Structure of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Papain-like Protease Bound to Ubiquitin Facilitates Targeted Disruption of Deubiquitinating Activity to Demonstrate Its Role in Innate Immune Suppression*
Auteurs : Ben A. Bailey-Elkin ; Robert C. M. Knaap ; Garrett G. Johnson ; Tim J. Dalebout ; Dennis K. Ninaber ; Puck B. Van Kasteren ; Peter J. Bredenbeek ; Eric J. Snijder ; Marjolein Kikkert ; Brian L. MarkSource :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2014.
Descripteurs français
- KwdFr :
- Cellules HEK293, Coronavirus du syndrome respiratoire du Moyen-Orient (enzymologie), Cristallographie aux rayons X, Domaine catalytique, Humains, Immunité innée, Modèles moléculaires, Motifs d'acides aminés, Mutagenèse, Mutation, Papaïne (), Papaïne (génétique), Papaïne (métabolisme), Tolérance immunitaire, Ubiquitine (), Ubiquitine (métabolisme), Ubiquitinylation.
- MESH :
- enzymologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- génétique : Papaïne.
- métabolisme : Papaïne, Ubiquitine.
- Cellules HEK293, Cristallographie aux rayons X, Domaine catalytique, Humains, Immunité innée, Modèles moléculaires, Motifs d'acides aminés, Mutagenèse, Mutation, Papaïne, Tolérance immunitaire, Ubiquitine, Ubiquitinylation.
English descriptors
- KwdEn :
- Amino Acid Motifs, Catalytic Domain, Crystallography, X-Ray, HEK293 Cells, Humans, Immune Tolerance, Immunity, Innate, Middle East Respiratory Syndrome Coronavirus (enzymology), Models, Molecular, Mutagenesis, Mutation, Papain (chemistry), Papain (genetics), Papain (metabolism), Ubiquitin (chemistry), Ubiquitin (metabolism), Ubiquitination.
- MESH :
- chemical , chemistry : Papain, Ubiquitin.
- enzymology : Middle East Respiratory Syndrome Coronavirus.
- chemical , genetics : Papain.
- chemical , metabolism : Papain, Ubiquitin.
- Amino Acid Motifs, Catalytic Domain, Crystallography, X-Ray, HEK293 Cells, Humans, Immune Tolerance, Immunity, Innate, Models, Molecular, Mutagenesis, Mutation, Ubiquitination.
Abstract
Url:
DOI: 10.1074/jbc.M114.609644
PubMed: 25320088
PubMed Central: 4263872
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PMC:4263872Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Crystal Structure of the Middle East Respiratory Syndrome Coronavirus
(MERS-CoV) Papain-like Protease Bound to Ubiquitin Facilitates Targeted
Disruption of Deubiquitinating Activity to Demonstrate Its Role in Innate Immune
Suppression<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Bailey Elkin, Ben A" sort="Bailey Elkin, Ben A" uniqKey="Bailey Elkin B" first="Ben A." last="Bailey-Elkin">Ben A. Bailey-Elkin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Knaap, Robert C M" sort="Knaap, Robert C M" uniqKey="Knaap R" first="Robert C. M." last="Knaap">Robert C. M. Knaap</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Johnson, Garrett G" sort="Johnson, Garrett G" uniqKey="Johnson G" first="Garrett G." last="Johnson">Garrett G. Johnson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Dalebout, Tim J" sort="Dalebout, Tim J" uniqKey="Dalebout T" first="Tim J." last="Dalebout">Tim J. Dalebout</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Ninaber, Dennis K" sort="Ninaber, Dennis K" uniqKey="Ninaber D" first="Dennis K." last="Ninaber">Dennis K. Ninaber</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></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><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Bredenbeek, Peter J" sort="Bredenbeek, Peter J" uniqKey="Bredenbeek P" first="Peter J." last="Bredenbeek">Peter J. Bredenbeek</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J." last="Snijder">Eric J. Snijder</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Kikkert, Marjolein" sort="Kikkert, Marjolein" uniqKey="Kikkert M" first="Marjolein" last="Kikkert">Marjolein Kikkert</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Mark, Brian L" sort="Mark, Brian L" uniqKey="Mark B" first="Brian L." last="Mark">Brian L. Mark</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25320088</idno><idno type="pmc">4263872</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263872</idno><idno type="RBID">PMC:4263872</idno><idno type="doi">10.1074/jbc.M114.609644</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000D86</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000D86</idno><idno type="wicri:Area/Pmc/Curation">000D86</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000D86</idno><idno type="wicri:Area/Pmc/Checkpoint">001111</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001111</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:25320088</idno><idno type="wicri:Area/PubMed/Corpus">001815</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001815</idno><idno type="wicri:Area/PubMed/Curation">001815</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001815</idno><idno type="wicri:Area/PubMed/Checkpoint">001951</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001951</idno><idno type="wicri:Area/Ncbi/Merge">000F32</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Crystal Structure of the Middle East Respiratory Syndrome Coronavirus
(MERS-CoV) Papain-like Protease Bound to Ubiquitin Facilitates Targeted
Disruption of Deubiquitinating Activity to Demonstrate Its Role in Innate Immune
Suppression<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Bailey Elkin, Ben A" sort="Bailey Elkin, Ben A" uniqKey="Bailey Elkin B" first="Ben A." last="Bailey-Elkin">Ben A. Bailey-Elkin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Knaap, Robert C M" sort="Knaap, Robert C M" uniqKey="Knaap R" first="Robert C. M." last="Knaap">Robert C. M. Knaap</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Johnson, Garrett G" sort="Johnson, Garrett G" uniqKey="Johnson G" first="Garrett G." last="Johnson">Garrett G. Johnson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Dalebout, Tim J" sort="Dalebout, Tim J" uniqKey="Dalebout T" first="Tim J." last="Dalebout">Tim J. Dalebout</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Ninaber, Dennis K" sort="Ninaber, Dennis K" uniqKey="Ninaber D" first="Dennis K." last="Ninaber">Dennis K. Ninaber</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></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><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Bredenbeek, Peter J" sort="Bredenbeek, Peter J" uniqKey="Bredenbeek P" first="Peter J." last="Bredenbeek">Peter J. Bredenbeek</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J." last="Snijder">Eric J. Snijder</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Kikkert, Marjolein" sort="Kikkert, Marjolein" uniqKey="Kikkert M" first="Marjolein" last="Kikkert">Marjolein Kikkert</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Mark, Brian L" sort="Mark, Brian L" uniqKey="Mark B" first="Brian L." last="Mark">Brian L. Mark</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Motifs</term><term>Catalytic Domain</term><term>Crystallography, X-Ray</term><term>HEK293 Cells</term><term>Humans</term><term>Immune Tolerance</term><term>Immunity, Innate</term><term>Middle East Respiratory Syndrome Coronavirus (enzymology)</term><term>Models, Molecular</term><term>Mutagenesis</term><term>Mutation</term><term>Papain (chemistry)</term><term>Papain (genetics)</term><term>Papain (metabolism)</term><term>Ubiquitin (chemistry)</term><term>Ubiquitin (metabolism)</term><term>Ubiquitination</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cellules HEK293</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (enzymologie)</term><term>Cristallographie aux rayons X</term><term>Domaine catalytique</term><term>Humains</term><term>Immunité innée</term><term>Modèles moléculaires</term><term>Motifs d'acides aminés</term><term>Mutagenèse</term><term>Mutation</term><term>Papaïne ()</term><term>Papaïne (génétique)</term><term>Papaïne (métabolisme)</term><term>Tolérance immunitaire</term><term>Ubiquitine ()</term><term>Ubiquitine (métabolisme)</term><term>Ubiquitinylation</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Papain</term><term>Ubiquitin</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Papain</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Papaïne</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Papain</term><term>Ubiquitin</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Papaïne</term><term>Ubiquitine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Motifs</term><term>Catalytic Domain</term><term>Crystallography, X-Ray</term><term>HEK293 Cells</term><term>Humans</term><term>Immune Tolerance</term><term>Immunity, Innate</term><term>Models, Molecular</term><term>Mutagenesis</term><term>Mutation</term><term>Ubiquitination</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules HEK293</term><term>Cristallographie aux rayons X</term><term>Domaine catalytique</term><term>Humains</term><term>Immunité innée</term><term>Modèles moléculaires</term><term>Motifs d'acides aminés</term><term>Mutagenèse</term><term>Mutation</term><term>Papaïne</term><term>Tolérance immunitaire</term><term>Ubiquitine</term><term>Ubiquitinylation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> MERS-CoV papain-like protease (PL<sup>pro</sup>)
processes viral polyproteins and has deubiquitinating activity.</p><p><bold>Results:</bold> A crystal structure of MERS-CoV PL<sup>pro</sup> bound to
ubiquitin guided mutagenesis to disrupt PL<sup>pro</sup> deubiquitinating
activity without affecting polyprotein cleavage.</p><p><bold>Conclusion:</bold> The deubiquitinating activity of MERS-CoV
PL<sup>pro</sup> suppresses the induction of interferon-β
expression.</p><p><bold>Significance:</bold> Our strategy to selectively disable PL<sup>pro</sup>deubiquitinating activity enables the study of its specific functions in
infection.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A. M. Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S. van Boheemen</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T. M. Bestebroer</name></author><author><name sortKey="Osterhaus, A D M E" uniqKey="Osterhaus A">A. D. M. E. Osterhaus</name></author><author><name sortKey="Fouchier, R A M" uniqKey="Fouchier R">R. A. M. Fouchier</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Azhar, E I" uniqKey="Azhar E">E. I. Azhar</name></author><author><name sortKey="El Kafrawy, S A" uniqKey="El Kafrawy S">S. A. El-Kafrawy</name></author><author><name sortKey="Farraj, S A" uniqKey="Farraj S">S. A. Farraj</name></author><author><name sortKey="Hassan, A M" uniqKey="Hassan A">A. M. 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(MERS-CoV) Papain-like Protease Bound to Ubiquitin Facilitates Targeted
Disruption of Deubiquitinating Activity to Demonstrate Its Role in Innate Immune
Suppression<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Bailey Elkin, Ben A" sort="Bailey Elkin, Ben A" uniqKey="Bailey Elkin B" first="Ben A." last="Bailey-Elkin">Ben A. Bailey-Elkin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Knaap, Robert C M" sort="Knaap, Robert C M" uniqKey="Knaap R" first="Robert C. M." last="Knaap">Robert C. M. Knaap</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Johnson, Garrett G" sort="Johnson, Garrett G" uniqKey="Johnson G" first="Garrett G." last="Johnson">Garrett G. Johnson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Dalebout, Tim J" sort="Dalebout, Tim J" uniqKey="Dalebout T" first="Tim J." last="Dalebout">Tim J. Dalebout</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Ninaber, Dennis K" sort="Ninaber, Dennis K" uniqKey="Ninaber D" first="Dennis K." last="Ninaber">Dennis K. Ninaber</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></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><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Bredenbeek, Peter J" sort="Bredenbeek, Peter J" uniqKey="Bredenbeek P" first="Peter J." last="Bredenbeek">Peter J. Bredenbeek</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J." last="Snijder">Eric J. Snijder</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Kikkert, Marjolein" sort="Kikkert, Marjolein" uniqKey="Kikkert M" first="Marjolein" last="Kikkert">Marjolein Kikkert</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Mark, Brian L" sort="Mark, Brian L" uniqKey="Mark B" first="Brian L." last="Mark">Brian L. Mark</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25320088</idno><idno type="pmc">4263872</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263872</idno><idno type="RBID">PMC:4263872</idno><idno type="doi">10.1074/jbc.M114.609644</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000D86</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000D86</idno><idno type="wicri:Area/Pmc/Curation">000D86</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000D86</idno><idno type="wicri:Area/Pmc/Checkpoint">001111</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001111</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Crystal Structure of the Middle East Respiratory Syndrome Coronavirus
(MERS-CoV) Papain-like Protease Bound to Ubiquitin Facilitates Targeted
Disruption of Deubiquitinating Activity to Demonstrate Its Role in Innate Immune
Suppression<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Bailey Elkin, Ben A" sort="Bailey Elkin, Ben A" uniqKey="Bailey Elkin B" first="Ben A." last="Bailey-Elkin">Ben A. Bailey-Elkin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Knaap, Robert C M" sort="Knaap, Robert C M" uniqKey="Knaap R" first="Robert C. M." last="Knaap">Robert C. M. Knaap</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Johnson, Garrett G" sort="Johnson, Garrett G" uniqKey="Johnson G" first="Garrett G." last="Johnson">Garrett G. Johnson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Dalebout, Tim J" sort="Dalebout, Tim J" uniqKey="Dalebout T" first="Tim J." last="Dalebout">Tim J. Dalebout</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Ninaber, Dennis K" sort="Ninaber, Dennis K" uniqKey="Ninaber D" first="Dennis K." last="Ninaber">Dennis K. Ninaber</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></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><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Bredenbeek, Peter J" sort="Bredenbeek, Peter J" uniqKey="Bredenbeek P" first="Peter J." last="Bredenbeek">Peter J. Bredenbeek</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J." last="Snijder">Eric J. Snijder</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Kikkert, Marjolein" sort="Kikkert, Marjolein" uniqKey="Kikkert M" first="Marjolein" last="Kikkert">Marjolein Kikkert</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Mark, Brian L" sort="Mark, Brian L" uniqKey="Mark B" first="Brian L." last="Mark">Brian L. Mark</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> MERS-CoV papain-like protease (PL<sup>pro</sup>)
processes viral polyproteins and has deubiquitinating activity.</p><p><bold>Results:</bold> A crystal structure of MERS-CoV PL<sup>pro</sup> bound to
ubiquitin guided mutagenesis to disrupt PL<sup>pro</sup> deubiquitinating
activity without affecting polyprotein cleavage.</p><p><bold>Conclusion:</bold> The deubiquitinating activity of MERS-CoV
PL<sup>pro</sup> suppresses the induction of interferon-β
expression.</p><p><bold>Significance:</bold> Our strategy to selectively disable PL<sup>pro</sup>deubiquitinating activity enables the study of its specific functions in
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DeLano</name></author></analytic></biblStruct></listBibl></div1></back></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Crystal structure of the Middle East respiratory syndrome coronavirus (MERS-CoV) papain-like protease bound to ubiquitin facilitates targeted disruption of deubiquitinating activity to demonstrate its role in innate immune suppression.</title><author><name sortKey="Bailey Elkin, Ben A" sort="Bailey Elkin, Ben A" uniqKey="Bailey Elkin B" first="Ben A" last="Bailey-Elkin">Ben A. Bailey-Elkin</name><affiliation wicri:level="4"><nlm:affiliation>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada and.</nlm:affiliation><country>Canada</country><wicri:regionArea>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Knaap, Robert C M" sort="Knaap, Robert C M" uniqKey="Knaap R" first="Robert C M" last="Knaap">Robert C M. Knaap</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Johnson, Garrett G" sort="Johnson, Garrett G" uniqKey="Johnson G" first="Garrett G" last="Johnson">Garrett G. Johnson</name><affiliation wicri:level="4"><nlm:affiliation>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada and.</nlm:affiliation><country>Canada</country><wicri:regionArea>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Dalebout, Tim J" sort="Dalebout, Tim J" uniqKey="Dalebout T" first="Tim J" last="Dalebout">Tim J. Dalebout</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Ninaber, Dennis K" sort="Ninaber, Dennis K" uniqKey="Ninaber D" first="Dennis K" last="Ninaber">Dennis K. Ninaber</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></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><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Bredenbeek, Peter J" sort="Bredenbeek, Peter J" uniqKey="Bredenbeek P" first="Peter J" last="Bredenbeek">Peter J. Bredenbeek</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J" last="Snijder">Eric J. Snijder</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Kikkert, Marjolein" sort="Kikkert, Marjolein" uniqKey="Kikkert M" first="Marjolein" last="Kikkert">Marjolein Kikkert</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands m.kikkert@lumc.nl.</nlm:affiliation><country wicri:rule="url">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Mark, Brian L" sort="Mark, Brian L" uniqKey="Mark B" first="Brian L" last="Mark">Brian L. Mark</name><affiliation wicri:level="4"><nlm:affiliation>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada and brian.mark@umanitoba.ca.</nlm:affiliation><country wicri:rule="url">Canada</country><wicri:regionArea>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25320088</idno><idno type="pmid">25320088</idno><idno type="doi">10.1074/jbc.M114.609644</idno><idno type="wicri:Area/PubMed/Corpus">001815</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001815</idno><idno type="wicri:Area/PubMed/Curation">001815</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001815</idno><idno type="wicri:Area/PubMed/Checkpoint">001951</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001951</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Crystal structure of the Middle East respiratory syndrome coronavirus (MERS-CoV) papain-like protease bound to ubiquitin facilitates targeted disruption of deubiquitinating activity to demonstrate its role in innate immune suppression.</title><author><name sortKey="Bailey Elkin, Ben A" sort="Bailey Elkin, Ben A" uniqKey="Bailey Elkin B" first="Ben A" last="Bailey-Elkin">Ben A. Bailey-Elkin</name><affiliation wicri:level="4"><nlm:affiliation>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada and.</nlm:affiliation><country>Canada</country><wicri:regionArea>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Knaap, Robert C M" sort="Knaap, Robert C M" uniqKey="Knaap R" first="Robert C M" last="Knaap">Robert C M. Knaap</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Johnson, Garrett G" sort="Johnson, Garrett G" uniqKey="Johnson G" first="Garrett G" last="Johnson">Garrett G. Johnson</name><affiliation wicri:level="4"><nlm:affiliation>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada and.</nlm:affiliation><country>Canada</country><wicri:regionArea>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Dalebout, Tim J" sort="Dalebout, Tim J" uniqKey="Dalebout T" first="Tim J" last="Dalebout">Tim J. Dalebout</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Ninaber, Dennis K" sort="Ninaber, Dennis K" uniqKey="Ninaber D" first="Dennis K" last="Ninaber">Dennis K. Ninaber</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></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><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Bredenbeek, Peter J" sort="Bredenbeek, Peter J" uniqKey="Bredenbeek P" first="Peter J" last="Bredenbeek">Peter J. Bredenbeek</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J" last="Snijder">Eric J. Snijder</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Kikkert, Marjolein" sort="Kikkert, Marjolein" uniqKey="Kikkert M" first="Marjolein" last="Kikkert">Marjolein Kikkert</name><affiliation wicri:level="1"><nlm:affiliation>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands m.kikkert@lumc.nl.</nlm:affiliation><country wicri:rule="url">Pays-Bas</country><wicri:regionArea>the Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden</wicri:regionArea><wicri:noRegion>2333 ZA Leiden</wicri:noRegion></affiliation></author><author><name sortKey="Mark, Brian L" sort="Mark, Brian L" uniqKey="Mark B" first="Brian L" last="Mark">Brian L. Mark</name><affiliation wicri:level="4"><nlm:affiliation>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada and brian.mark@umanitoba.ca.</nlm:affiliation><country wicri:rule="url">Canada</country><wicri:regionArea>From the Department of Microbiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="eISSN">1083-351X</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Motifs</term><term>Catalytic Domain</term><term>Crystallography, X-Ray</term><term>HEK293 Cells</term><term>Humans</term><term>Immune Tolerance</term><term>Immunity, Innate</term><term>Middle East Respiratory Syndrome Coronavirus (enzymology)</term><term>Models, Molecular</term><term>Mutagenesis</term><term>Mutation</term><term>Papain (chemistry)</term><term>Papain (genetics)</term><term>Papain (metabolism)</term><term>Ubiquitin (chemistry)</term><term>Ubiquitin (metabolism)</term><term>Ubiquitination</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cellules HEK293</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (enzymologie)</term><term>Cristallographie aux rayons X</term><term>Domaine catalytique</term><term>Humains</term><term>Immunité innée</term><term>Modèles moléculaires</term><term>Motifs d'acides aminés</term><term>Mutagenèse</term><term>Mutation</term><term>Papaïne ()</term><term>Papaïne (génétique)</term><term>Papaïne (métabolisme)</term><term>Tolérance immunitaire</term><term>Ubiquitine ()</term><term>Ubiquitine (métabolisme)</term><term>Ubiquitinylation</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Papain</term><term>Ubiquitin</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Papain</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Papaïne</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Papain</term><term>Ubiquitin</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Papaïne</term><term>Ubiquitine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Motifs</term><term>Catalytic Domain</term><term>Crystallography, X-Ray</term><term>HEK293 Cells</term><term>Humans</term><term>Immune Tolerance</term><term>Immunity, Innate</term><term>Models, Molecular</term><term>Mutagenesis</term><term>Mutation</term><term>Ubiquitination</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules HEK293</term><term>Cristallographie aux rayons X</term><term>Domaine catalytique</term><term>Humains</term><term>Immunité innée</term><term>Modèles moléculaires</term><term>Motifs d'acides aminés</term><term>Mutagenèse</term><term>Mutation</term><term>Papaïne</term><term>Tolérance immunitaire</term><term>Ubiquitine</term><term>Ubiquitinylation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging human pathogen that was first isolated in 2012. MERS-CoV replication depends in part on a virus-encoded papain-like protease (PL(pro)) that cleaves the viral replicase polyproteins at three sites releasing non-structural protein 1 (nsp1), nsp2, and nsp3. In addition to this replicative function, MERS-CoV PL(pro) was recently shown to be a deubiquitinating enzyme (DUB) and to possess deISGylating activity, as previously reported for other coronaviral PL(pro) domains, including that of severe acute respiratory syndrome coronavirus. These activities have been suggested to suppress host antiviral responses during infection. To understand the molecular basis for ubiquitin (Ub) recognition and deconjugation by MERS-CoV PL(pro), we determined its crystal structure in complex with Ub. Guided by this structure, mutations were introduced into PL(pro) to specifically disrupt Ub binding without affecting viral polyprotein cleavage, as determined using an in trans nsp3↓4 cleavage assay. Having developed a strategy to selectively disable PL(pro) DUB activity, we were able to specifically examine the effects of this activity on the innate immune response. Whereas the wild-type PL(pro) domain was found to suppress IFN-β promoter activation, PL(pro) variants specifically lacking DUB activity were no longer able to do so. These findings directly implicate the DUB function of PL(pro), and not its proteolytic activity per se, in the inhibition of IFN-β promoter activity. The ability to decouple the DUB activity of PL(pro) from its role in viral polyprotein processing now provides an approach to further dissect the role(s) of PL(pro) as a viral DUB during MERS-CoV infection. </div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Crystal Structure of the Middle East Respiratory Syndrome Coronavirus
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