Structural and functional characterization of MERS coronavirus papain-like protease
Identifieur interne : 000F67 ( Pmc/Checkpoint ); précédent : 000F66; suivant : 000F68Structural and functional characterization of MERS coronavirus papain-like protease
Auteurs : Min-Han Lin [Taïwan] ; Shang-Ju Chuang [Taïwan] ; Chiao-Che Chen [Taïwan] ; Shu-Chun Cheng [Taïwan] ; Kai-Wen Cheng [Taïwan] ; Chao-Hsiung Lin [Taïwan] ; Chiao-Yin Sun [Taïwan] ; Chi-Yuan Chou [Taïwan]Source :
- Journal of Biomedical Science [ 1021-7770 ] ; 2014.
Abstract
A new highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and Saudi Arabia and quickly spread to some European countries since September 2012. Until 15 May 2014, it has infected at least 572 people with a fatality rate of about 30% globally. Studies to understand the virus and to develop antiviral drugs or therapy are necessary and urgent. In the present study, MERS-CoV papain-like protease (PLpro) is expressed, and its structural and functional consequences are elucidated.
Circular dichroism and Tyr/Trp fluorescence analyses indicated that the secondary and tertiary structure of MERS-CoV PLpro is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PLpro is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PLpro exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PLpro. A natural mutation, Leu105, is the major reason for this difference.
Overall, MERS-CoV PLpro bound by an endogenous metal ion shows a folded structure and potent proteolytic and deubiquitination activity. These findings provide important insights into the structural and functional properties of coronaviral PLpro family, which is applicable to develop strategies inhibiting PLpro against highly pathogenic coronaviruses.
The online version of this article (doi:10.1186/1423-0127-21-54) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/1423-0127-21-54
PubMed: 24898546
PubMed Central: 4051379
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sort="Chuang, Shang Ju" uniqKey="Chuang S" first="Shang-Ju" last="Chuang">Shang-Ju Chuang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.260770.4</institution-id><institution-id institution-id-type="ISNI">0000000104255914</institution-id><institution>Department of Life Sciences and Institute of Genome Sciences,</institution><institution>National Yang-Ming University,</institution></institution-wrap>Taipei, 112 Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Taipei</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Chiao Che" sort="Chen, Chiao Che" uniqKey="Chen C" first="Chiao-Che" last="Chen">Chiao-Che Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.260770.4</institution-id><institution-id institution-id-type="ISNI">0000000104255914</institution-id><institution>Department of Life Sciences and 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id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.260770.4</institution-id><institution-id institution-id-type="ISNI">0000000104255914</institution-id><institution>Department of Life Sciences and Institute of Genome Sciences,</institution><institution>National Yang-Ming University,</institution></institution-wrap>Taipei, 112 Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Taipei</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Biomedical Science</title><idno type="ISSN">1021-7770</idno><idno type="eISSN">1423-0127</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Backgrounds</title><p>A new highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and Saudi Arabia and quickly spread to some European countries since September 2012. Until 15 May 2014, it has infected at least 572 people with a fatality rate of about 30% globally. Studies to understand the virus and to develop antiviral drugs or therapy are necessary and urgent. In the present study, MERS-CoV papain-like protease (PL<sup>pro</sup>) is expressed, and its structural and functional consequences are elucidated.</p></sec><sec><title>Results</title><p>Circular dichroism and Tyr/Trp fluorescence analyses indicated that the secondary and tertiary structure of MERS-CoV PL<sup>pro</sup> is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PL<sup>pro</sup> is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PL<sup>pro</sup> exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PL<sup>pro</sup>. A natural mutation, Leu105, is the major reason for this difference.</p></sec><sec><title>Conclusions</title><p>Overall, MERS-CoV PL<sup>pro</sup> bound by an endogenous metal ion shows a folded structure and potent proteolytic and deubiquitination activity. These findings provide important insights into the structural and functional properties of coronaviral PL<sup>pro</sup> family, which is applicable to develop strategies inhibiting PL<sup>pro</sup> against highly pathogenic coronaviruses.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/1423-0127-21-54) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Anderson, Lj" uniqKey="Anderson L">LJ Anderson</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Jf" uniqKey="Chan J">JF Chan</name></author><author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name></author><author><name sortKey="To, Kk" uniqKey="To K">KK To</name></author><author><name sortKey="Cheng, Vc" uniqKey="Cheng V">VC 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Biomed Sci</journal-id><journal-id journal-id-type="iso-abbrev">J. Biomed. Sci</journal-id><journal-title-group><journal-title>Journal of Biomedical Science</journal-title></journal-title-group><issn pub-type="ppub">1021-7770</issn><issn pub-type="epub">1423-0127</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24898546</article-id><article-id pub-id-type="pmc">4051379</article-id><article-id pub-id-type="publisher-id">588</article-id><article-id pub-id-type="doi">10.1186/1423-0127-21-54</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research</subject></subj-group></article-categories><title-group><article-title>Structural and functional characterization of MERS coronavirus papain-like protease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lin</surname><given-names>Min-Han</given-names></name><address><email>hantingpay@gmail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chuang</surname><given-names>Shang-Ju</given-names></name><address><email>aspapsasp@hotmail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Chiao-Che</given-names></name><address><email>march1990324@gmail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Shu-Chun</given-names></name><address><email>sama3665@hotmail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Kai-Wen</given-names></name><address><email>kevintzang@hotmail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Lin</surname><given-names>Chao-Hsiung</given-names></name><address><email>chlin2@ym.edu.tw</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Sun</surname><given-names>Chiao-Yin</given-names></name><address><email>fish3970@gmail.com</email></address><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Chou</surname><given-names>Chi-Yuan</given-names></name><address><email>cychou@ym.edu.tw</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="GRID">grid.260770.4</institution-id><institution-id institution-id-type="ISNI">0000000104255914</institution-id><institution>Department of Life Sciences and Institute of Genome Sciences,</institution><institution>National Yang-Ming University,</institution></institution-wrap>Taipei, 112 Taiwan</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="GRID">grid.454209.e</institution-id><institution-id institution-id-type="ISNI">0000000406392551</institution-id><institution>Department of Nephrology,</institution><institution>Chang-Gung Memorial Hospital,</institution></institution-wrap>Keelung, 204 Taiwan</aff></contrib-group><pub-date pub-type="epub"><day>4</day><month>6</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>4</day><month>6</month><year>2014</year></pub-date><pub-date pub-type="collection"><year>2014</year></pub-date><volume>21</volume><elocation-id>54</elocation-id><history><date date-type="received"><day>23</day><month>4</month><year>2014</year></date><date date-type="accepted"><day>19</day><month>5</month><year>2014</year></date></history><permissions><copyright-statement>© Lin et al.; licensee BioMed Central Ltd. 2014</copyright-statement><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract id="Abs1"><sec><title>Backgrounds</title><p>A new highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and Saudi Arabia and quickly spread to some European countries since September 2012. Until 15 May 2014, it has infected at least 572 people with a fatality rate of about 30% globally. Studies to understand the virus and to develop antiviral drugs or therapy are necessary and urgent. In the present study, MERS-CoV papain-like protease (PL<sup>pro</sup>) is expressed, and its structural and functional consequences are elucidated.</p></sec><sec><title>Results</title><p>Circular dichroism and Tyr/Trp fluorescence analyses indicated that the secondary and tertiary structure of MERS-CoV PL<sup>pro</sup> is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PL<sup>pro</sup> is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PL<sup>pro</sup> exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PL<sup>pro</sup>. A natural mutation, Leu105, is the major reason for this difference.</p></sec><sec><title>Conclusions</title><p>Overall, MERS-CoV PL<sup>pro</sup> bound by an endogenous metal ion shows a folded structure and potent proteolytic and deubiquitination activity. These findings provide important insights into the structural and functional properties of coronaviral PL<sup>pro</sup> family, which is applicable to develop strategies inhibiting PL<sup>pro</sup> against highly pathogenic coronaviruses.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/1423-0127-21-54) contains supplementary material, which is available to authorized users.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>MERS coronavirus</kwd><kwd>Papain-like protease</kwd><kwd>Deubiquitination</kwd><kwd>Antiviral target</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2014</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>Taïwan</li></country></list><tree><country name="Taïwan"><noRegion><name sortKey="Lin, Min Han" sort="Lin, Min Han" uniqKey="Lin M" first="Min-Han" last="Lin">Min-Han Lin</name></noRegion><name sortKey="Chen, Chiao Che" sort="Chen, Chiao Che" uniqKey="Chen C" first="Chiao-Che" last="Chen">Chiao-Che Chen</name><name sortKey="Cheng, Kai Wen" sort="Cheng, Kai Wen" uniqKey="Cheng K" first="Kai-Wen" last="Cheng">Kai-Wen Cheng</name><name sortKey="Cheng, Shu Chun" sort="Cheng, Shu Chun" uniqKey="Cheng S" first="Shu-Chun" last="Cheng">Shu-Chun Cheng</name><name sortKey="Chou, Chi Yuan" sort="Chou, Chi Yuan" uniqKey="Chou C" first="Chi-Yuan" last="Chou">Chi-Yuan Chou</name><name sortKey="Chuang, Shang Ju" sort="Chuang, Shang Ju" uniqKey="Chuang S" first="Shang-Ju" last="Chuang">Shang-Ju Chuang</name><name sortKey="Lin, Chao Hsiung" sort="Lin, Chao Hsiung" uniqKey="Lin C" first="Chao-Hsiung" last="Lin">Chao-Hsiung Lin</name><name sortKey="Sun, Chiao Yin" sort="Sun, Chiao Yin" uniqKey="Sun C" first="Chiao-Yin" last="Sun">Chiao-Yin Sun</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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