Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2'-O-methylation by nsp16/nsp10 protein complex.
Identifieur interne : 002149 ( Main/Exploration ); précédent : 002148; suivant : 002150Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2'-O-methylation by nsp16/nsp10 protein complex.
Auteurs : Yu Chen [République populaire de Chine] ; Ceyang Su ; Min Ke ; Xu Jin ; Lirong Xu ; Zhou Zhang ; Andong Wu ; Ying Sun ; Zhouning Yang ; Po Tien ; Tero Ahola ; Yi Liang ; Xinqi Liu ; Deyin GuoSource :
- PLoS pathogens [ 1553-7374 ] ; 2011.
Descripteurs français
- KwdFr :
- ARN viral (génétique), ARN viral (métabolisme), Adémétionine (métabolisme), Analogues des coiffes des ARN (métabolisme), Coiffes des ARN (), Coiffes des ARN (métabolisme), Cristallographie aux rayons X, Données de séquences moléculaires, Liaison aux protéines, Methyltransferases (), Methyltransferases (génétique), Methyltransferases (métabolisme), Modèles moléculaires, Méthylation, Protéines virales non structurales (), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), Structure secondaire des protéines, Structure tertiaire des protéines, Virus du SRAS (génétique), Virus du SRAS (métabolisme).
- MESH :
- génétique : ARN viral, Methyltransferases, Protéines virales non structurales, Virus du SRAS.
- métabolisme : ARN viral, Adémétionine, Analogues des coiffes des ARN, Coiffes des ARN, Methyltransferases, Protéines virales non structurales, Virus du SRAS.
- Coiffes des ARN, Cristallographie aux rayons X, Données de séquences moléculaires, Liaison aux protéines, Methyltransferases, Modèles moléculaires, Méthylation, Protéines virales non structurales, Structure secondaire des protéines, Structure tertiaire des protéines.
English descriptors
- KwdEn :
- Crystallography, X-Ray, Methylation, Methyltransferases (chemistry), Methyltransferases (genetics), Methyltransferases (metabolism), Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, RNA Cap Analogs (metabolism), RNA Caps (chemistry), RNA Caps (metabolism), RNA, Viral (genetics), RNA, Viral (metabolism), S-Adenosylmethionine (metabolism), SARS Virus (genetics), SARS Virus (metabolism), Viral Nonstructural Proteins (chemistry), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism).
- MESH :
- chemical , chemistry : Methyltransferases, RNA Caps, Viral Nonstructural Proteins.
- chemical , genetics : Methyltransferases, RNA, Viral, Viral Nonstructural Proteins.
- chemical , metabolism : Methyltransferases, RNA Cap Analogs, RNA Caps, RNA, Viral, S-Adenosylmethionine, Viral Nonstructural Proteins.
- genetics : SARS Virus.
- metabolism : SARS Virus.
- Crystallography, X-Ray, Methylation, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary.
Abstract
The 5'-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5'-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2'-O positions, catalyzed by nsp14 N7-MTase and nsp16 2'-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2'-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs.
DOI: 10.1371/journal.ppat.1002294
PubMed: 22022266
Affiliations:
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China.</nlm:affiliation><orgName type="university">Université de Wuhan</orgName><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="province">Hubei</region></placeName></affiliation></author><author><name sortKey="Su, Ceyang" sort="Su, Ceyang" uniqKey="Su C" first="Ceyang" last="Su">Ceyang Su</name></author><author><name sortKey="Ke, Min" sort="Ke, Min" uniqKey="Ke M" first="Min" last="Ke">Min Ke</name></author><author><name sortKey="Jin, Xu" sort="Jin, Xu" uniqKey="Jin X" first="Xu" last="Jin">Xu Jin</name></author><author><name sortKey="Xu, Lirong" sort="Xu, Lirong" uniqKey="Xu L" first="Lirong" last="Xu">Lirong Xu</name></author><author><name sortKey="Zhang, Zhou" sort="Zhang, Zhou" uniqKey="Zhang Z" first="Zhou" last="Zhang">Zhou Zhang</name></author><author><name sortKey="Wu, Andong" sort="Wu, Andong" uniqKey="Wu A" first="Andong" last="Wu">Andong Wu</name></author><author><name sortKey="Sun, Ying" sort="Sun, Ying" 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xml:lang="fr"><term>ARN viral (génétique)</term><term>ARN viral (métabolisme)</term><term>Adémétionine (métabolisme)</term><term>Analogues des coiffes des ARN (métabolisme)</term><term>Coiffes des ARN ()</term><term>Coiffes des ARN (métabolisme)</term><term>Cristallographie aux rayons X</term><term>Données de séquences moléculaires</term><term>Liaison aux protéines</term><term>Methyltransferases ()</term><term>Methyltransferases (génétique)</term><term>Methyltransferases (métabolisme)</term><term>Modèles moléculaires</term><term>Méthylation</term><term>Protéines virales non structurales ()</term><term>Protéines virales non structurales (génétique)</term><term>Protéines virales non structurales (métabolisme)</term><term>Structure secondaire des protéines</term><term>Structure tertiaire des protéines</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Methyltransferases</term><term>RNA Caps</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Methyltransferases</term><term>RNA, Viral</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Methyltransferases</term><term>RNA Cap Analogs</term><term>RNA Caps</term><term>RNA, Viral</term><term>S-Adenosylmethionine</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN viral</term><term>Methyltransferases</term><term>Protéines virales non structurales</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN viral</term><term>Adémétionine</term><term>Analogues des coiffes des ARN</term><term>Coiffes des ARN</term><term>Methyltransferases</term><term>Protéines virales non structurales</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Crystallography, X-Ray</term><term>Methylation</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Protein Binding</term><term>Protein Structure, Secondary</term><term>Protein Structure, Tertiary</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Coiffes des ARN</term><term>Cristallographie aux rayons X</term><term>Données de séquences moléculaires</term><term>Liaison aux protéines</term><term>Methyltransferases</term><term>Modèles moléculaires</term><term>Méthylation</term><term>Protéines virales non structurales</term><term>Structure secondaire des protéines</term><term>Structure tertiaire des protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The 5'-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5'-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2'-O positions, catalyzed by nsp14 N7-MTase and nsp16 2'-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2'-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Hubei</li></region><settlement><li>Wuhan</li></settlement><orgName><li>Université de Wuhan</li></orgName></list><tree><noCountry><name sortKey="Ahola, Tero" sort="Ahola, Tero" uniqKey="Ahola T" first="Tero" last="Ahola">Tero Ahola</name><name sortKey="Guo, Deyin" sort="Guo, Deyin" uniqKey="Guo D" first="Deyin" last="Guo">Deyin Guo</name><name sortKey="Jin, Xu" sort="Jin, Xu" uniqKey="Jin X" first="Xu" last="Jin">Xu Jin</name><name sortKey="Ke, Min" sort="Ke, Min" uniqKey="Ke M" first="Min" last="Ke">Min Ke</name><name sortKey="Liang, Yi" sort="Liang, Yi" uniqKey="Liang Y" first="Yi" last="Liang">Yi Liang</name><name sortKey="Liu, Xinqi" sort="Liu, Xinqi" uniqKey="Liu X" first="Xinqi" last="Liu">Xinqi Liu</name><name sortKey="Su, Ceyang" sort="Su, Ceyang" uniqKey="Su C" first="Ceyang" last="Su">Ceyang Su</name><name sortKey="Sun, Ying" sort="Sun, Ying" uniqKey="Sun Y" first="Ying" last="Sun">Ying Sun</name><name sortKey="Tien, Po" sort="Tien, Po" uniqKey="Tien P" first="Po" last="Tien">Po Tien</name><name sortKey="Wu, Andong" sort="Wu, Andong" uniqKey="Wu A" first="Andong" last="Wu">Andong Wu</name><name sortKey="Xu, Lirong" sort="Xu, Lirong" uniqKey="Xu L" first="Lirong" last="Xu">Lirong Xu</name><name sortKey="Yang, Zhouning" sort="Yang, Zhouning" uniqKey="Yang Z" first="Zhouning" last="Yang">Zhouning Yang</name><name sortKey="Zhang, Zhou" sort="Zhang, Zhou" uniqKey="Zhang Z" first="Zhou" last="Zhang">Zhou Zhang</name></noCountry><country name="République populaire de Chine"><region name="Hubei"><name sortKey="Chen, Yu" sort="Chen, Yu" uniqKey="Chen Y" first="Yu" last="Chen">Yu Chen</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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