SrasV1, Main, Curation, bibRecord, 003457

Without Its N-Finger, the Main Protease of Severe Acute Respiratory Syndrome Coronavirus Can Form a Novel Dimer through Its C-Terminal Domain

Identifieur interne : 003457 ( Main/Curation ); précédent : 003456; suivant : 003458

Without Its N-Finger, the Main Protease of Severe Acute Respiratory Syndrome Coronavirus Can Form a Novel Dimer through Its C-Terminal Domain

Auteurs : NAN ZHONG [République populaire de Chine] ; SHENGNAN ZHANG [République populaire de Chine] ; PENG ZOU [République populaire de Chine] ; JIAXUAN CHEN [République populaire de Chine] ; XUE KANG [République populaire de Chine] ; ZHE LI [République populaire de Chine] ; CHAO LIANG [République populaire de Chine] ; CHANGWEN JIN [République populaire de Chine] ; BIN XIA [République populaire de Chine]

Source :

Journal of virology [ 0022-538X ] ; 2008.

RBID : Pascal:08-0228459

Descripteurs français

Pascal (Inist)
- Coronavirus, Virologie, Syndrome respiratoire aigu sévère.

English descriptors

KwdEn :
- Coronavirus, Severe acute respiratory syndrome, Virology.

Abstract

The main protease (M^pro) of severe acute respiratory syndrome coronavirus (SARS-CoV) plays an essential role in the extensive proteolytic processing of the viral polyproteins (ppla and pplab), and it is an important target for anti-SARS drug development. It was found that SARS-CoV M^pro exists in solution as an equilibrium of both monomeric and dimeric forms, and the dimeric form is the enzymatically active form. However, the mechanism of SARS-CoV M^pro dimerization, especially the roles of its N-terminal seven residues (N-finger) and its unique C-terminal domain in the dimerization, remain unclear. Here we report that the SARS-CoV M^pro C-terminal domain alone (residues 187 to 306; M^pro-C) is produced in Escherichia coli in both monomeric and dimeric forms, and no exchange could be observed between them at room temperature. The M^pro-C dimer has a novel dimerization interface. Meanwhile, the N-finger deletion mutant of SARS-CoV M^pro also exists as both a stable monomer and a stable dimer, and the dimer is formed through the same C-terminal-domain interaction as that in the M^pro-C dimer. However, no C-terminal domain-mediated dimerization form can be detected for wild-type SARS-CoV M^pro. Our study results help to clarify previously published controversial claims about the role of the N-finger in SARS-CoV M^pro dimerization. Apparently, without the N-finger, SARS-CoV M^pro can no longer retain the active dimer structure; instead, it can form a new type of dimer which is inactive. Therefore, the N-finger of SARS-CoV M^pro is not only critical for its dimerization but also essential for the enzyme to form the enzymatically active dimer.

Links toward previous steps (curation, corpus...)

to stream PascalFrancis, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000291
to stream PascalFrancis, to step Curation: Pour aller vers cette notice dans l'étape Curation :000697
to stream PascalFrancis, to step Checkpoint: Pour aller vers cette notice dans l'étape Curation :000234
to stream Main, to step Merge: Pour aller vers cette notice dans l'étape Curation :003560

Links to Exploration step

Pascal:08-0228459

Le document en format XML

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<author><name sortKey="Peng Zou" sort="Peng Zou" uniqKey="Peng Zou" last="Peng Zou">PENG ZOU</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Beijing Nuclear Magnetic Resonance Center, Peking University</s1>
<s2>Beijing 100871</s2>
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<placeName><settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>College of Chemistry and Molecular Engineering, Peking University</s1>
<s2>Beijing 100871</s2>
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<placeName><settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jiaxuan Chen" sort="Jiaxuan Chen" uniqKey="Jiaxuan Chen" last="Jiaxuan Chen">JIAXUAN CHEN</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Beijing Nuclear Magnetic Resonance Center, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
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<country>République populaire de Chine</country>
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</placeName>
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<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="03"><s1>College of Life Science, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
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</inist:fA14>
<country>République populaire de Chine</country>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Xue Kang" sort="Xue Kang" uniqKey="Xue Kang" last="Xue Kang">XUE KANG</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Beijing Nuclear Magnetic Resonance Center, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<country>République populaire de Chine</country>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>College of Chemistry and Molecular Engineering, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
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<country>République populaire de Chine</country>
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<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zhe Li" sort="Zhe Li" uniqKey="Zhe Li" last="Zhe Li">ZHE LI</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Beijing Nuclear Magnetic Resonance Center, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<country>République populaire de Chine</country>
<placeName><settlement type="city">Pékin</settlement>
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<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="03"><s1>College of Life Science, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
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<country>République populaire de Chine</country>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
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<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chao Liang" sort="Chao Liang" uniqKey="Chao Liang" last="Chao Liang">CHAO LIANG</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Beijing Nuclear Magnetic Resonance Center, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<country>République populaire de Chine</country>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Changwen Jin" sort="Changwen Jin" uniqKey="Changwen Jin" last="Changwen Jin">CHANGWEN JIN</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Beijing Nuclear Magnetic Resonance Center, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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</inist:fA14>
<country>République populaire de Chine</country>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>College of Chemistry and Molecular Engineering, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="03"><s1>College of Life Science, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bin Xia" sort="Bin Xia" uniqKey="Bin Xia" last="Bin Xia">BIN XIA</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Beijing Nuclear Magnetic Resonance Center, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>College of Chemistry and Molecular Engineering, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="03"><s1>College of Life Science, Peking University</s1>
<s2>Beijing 100871</s2>
<s3>CHN</s3>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
<placeName><settlement type="city">Pékin</settlement>
<region type="capitale">Pékin</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
<imprint><date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus</term>
<term>Severe acute respiratory syndrome</term>
<term>Virology</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term>
<term>Virologie</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The main protease (M<sup>pro</sup>
) of severe acute respiratory syndrome coronavirus (SARS-CoV) plays an essential role in the extensive proteolytic processing of the viral polyproteins (ppla and pplab), and it is an important target for anti-SARS drug development. It was found that SARS-CoV M<sup>pro</sup>
 exists in solution as an equilibrium of both monomeric and dimeric forms, and the dimeric form is the enzymatically active form. However, the mechanism of SARS-CoV M<sup>pro</sup>
 dimerization, especially the roles of its N-terminal seven residues (N-finger) and its unique C-terminal domain in the dimerization, remain unclear. Here we report that the SARS-CoV M<sup>pro</sup>
 C-terminal domain alone (residues 187 to 306; M<sup>pro</sup>
-C) is produced in Escherichia coli in both monomeric and dimeric forms, and no exchange could be observed between them at room temperature. The M<sup>pro</sup>
-C dimer has a novel dimerization interface. Meanwhile, the N-finger deletion mutant of SARS-CoV M<sup>pro</sup>
 also exists as both a stable monomer and a stable dimer, and the dimer is formed through the same C-terminal-domain interaction as that in the M<sup>pro</sup>
-C dimer. However, no C-terminal domain-mediated dimerization form can be detected for wild-type SARS-CoV M<sup>pro</sup>
. Our study results help to clarify previously published controversial claims about the role of the N-finger in SARS-CoV M<sup>pro</sup>
 dimerization. Apparently, without the N-finger, SARS-CoV M<sup>pro</sup>
 can no longer retain the active dimer structure; instead, it can form a new type of dimer which is inactive. Therefore, the N-finger of SARS-CoV M<sup>pro</sup>
 is not only critical for its dimerization but also essential for the enzyme to form the enzymatically active dimer.</div>
</front>
</TEI>
</record>

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Without Its N-Finger, the Main Protease of Severe Acute Respiratory Syndrome Coronavirus Can Form a Novel Dimer through Its C-Terminal Domain

Without Its N-Finger, the Main Protease of Severe Acute Respiratory Syndrome Coronavirus Can Form a Novel Dimer through Its C-Terminal Domain

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