Structural basis and functional analysis of the SARS coronavirus nsp14-nsp10 complex.
Identifieur interne : 001241 ( Main/Exploration ); précédent : 001240; suivant : 001242Structural basis and functional analysis of the SARS coronavirus nsp14-nsp10 complex.
Auteurs : Yuanyuan Ma [République populaire de Chine] ; Lijie Wu [République populaire de Chine] ; Neil Shaw [République populaire de Chine] ; Yan Gao [République populaire de Chine] ; Jin Wang [République populaire de Chine] ; Yuna Sun [République populaire de Chine] ; Zhiyong Lou [République populaire de Chine] ; Liming Yan [République populaire de Chine] ; Rongguang Zhang [République populaire de Chine] ; Zihe Rao [République populaire de Chine]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2015.
Descripteurs français
- KwdFr :
- ARN messager (génétique), ARN viral (génétique), Doigts de zinc, Données de séquences moléculaires, Escherichia coli (métabolisme), Exoribonucleases (), Ligands, Methyltransferases (), Modèles moléculaires, Protéines virales non structurales (), Réplication virale (génétique), Similitude de séquences d'acides aminés, Structure secondaire des protéines, Structure tertiaire des protéines, Séquence d'acides aminés, Virus du SRAS ().
- MESH :
- génétique : ARN messager, ARN viral, Réplication virale.
- métabolisme : Escherichia coli.
- Doigts de zinc, Données de séquences moléculaires, Exoribonucleases, Ligands, Methyltransferases, Modèles moléculaires, Protéines virales non structurales, Similitude de séquences d'acides aminés, Structure secondaire des protéines, Structure tertiaire des protéines, Séquence d'acides aminés, Virus du SRAS.
English descriptors
- KwdEn :
- Amino Acid Sequence, Escherichia coli (metabolism), Exoribonucleases (chemistry), Ligands, Methyltransferases (chemistry), Models, Molecular, Molecular Sequence Data, Protein Structure, Secondary, Protein Structure, Tertiary, RNA, Messenger (genetics), RNA, Viral (genetics), SARS Virus (chemistry), Sequence Homology, Amino Acid, Viral Nonstructural Proteins (chemistry), Virus Replication (genetics), Zinc Fingers.
- MESH :
- chemical , chemistry : Exoribonucleases, Methyltransferases, Viral Nonstructural Proteins.
- chemical , genetics : RNA, Messenger, RNA, Viral.
- chemistry : SARS Virus.
- genetics : Virus Replication.
- metabolism : Escherichia coli.
- Amino Acid Sequence, Ligands, Models, Molecular, Molecular Sequence Data, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Zinc Fingers.
Abstract
Nonstructural protein 14 (nsp14) of coronaviruses (CoV) is important for viral replication and transcription. The N-terminal exoribonuclease (ExoN) domain plays a proofreading role for prevention of lethal mutagenesis, and the C-terminal domain functions as a (guanine-N7) methyl transferase (N7-MTase) for mRNA capping. The molecular basis of both these functions is unknown. Here, we describe crystal structures of severe acute respiratory syndrome (SARS)-CoV nsp14 in complex with its activator nonstructural protein10 (nsp10) and functional ligands. One molecule of nsp10 interacts with ExoN of nsp14 to stabilize it and stimulate its activity. Although the catalytic core of nsp14 ExoN is reminiscent of proofreading exonucleases, the presence of two zinc fingers sets it apart from homologs. Mutagenesis studies indicate that both these zinc fingers are essential for the function of nsp14. We show that a DEEDh (the five catalytic amino acids) motif drives nucleotide excision. The N7-MTase domain exhibits a noncanonical MTase fold with a rare β-sheet insertion and a peripheral zinc finger. The cap-precursor guanosine-P3-adenosine-5',5'-triphosphate and S-adenosyl methionine bind in proximity in a highly constricted pocket between two β-sheets to accomplish methyl transfer. Our studies provide the first glimpses, to our knowledge, into the architecture of the nsp14-nsp10 complex involved in RNA viral proofreading.
DOI: 10.1073/pnas.1508686112
PubMed: 26159422
Affiliations:
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National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; raozh@mail.tsinghua.edu.cn rzhang@sun5.ibp.ac.cn.</nlm:affiliation><country wicri:rule="url">République populaire de Chine</country><wicri:regionArea>National Center for Protein Science Shanghai, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Rao, Zihe" sort="Rao, Zihe" uniqKey="Rao Z" first="Zihe" last="Rao">Zihe Rao</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; National Center for Protein Science Shanghai, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; 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Collaborative Innovation Center for Biotherapy Chengdu, Sichuan 610041, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu, Sichuan 610041, China; Collaborative Innovation Center for Biotherapy Chengdu, Sichuan 610041</wicri:regionArea><wicri:noRegion>Sichuan 610041</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Yuna" sort="Sun, Yuna" uniqKey="Sun Y" first="Yuna" last="Sun">Yuna Sun</name><affiliation wicri:level="1"><nlm:affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Lou, Zhiyong" sort="Lou, Zhiyong" uniqKey="Lou Z" first="Zhiyong" last="Lou">Zhiyong Lou</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Yan, Liming" sort="Yan, Liming" uniqKey="Yan L" first="Liming" last="Yan">Liming Yan</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Laboratory of Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Rongguang" sort="Zhang, Rongguang" uniqKey="Zhang R" first="Rongguang" last="Zhang">Rongguang Zhang</name><affiliation wicri:level="1"><nlm:affiliation>National Center for Protein Science Shanghai, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; raozh@mail.tsinghua.edu.cn rzhang@sun5.ibp.ac.cn.</nlm:affiliation><country wicri:rule="url">République populaire de Chine</country><wicri:regionArea>National Center for Protein Science Shanghai, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Rao, Zihe" sort="Rao, Zihe" uniqKey="Rao Z" first="Zihe" last="Rao">Zihe Rao</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; National Center for Protein Science Shanghai, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu, Sichuan 610041, China; Collaborative Innovation Center for Biotherapy Chengdu, Sichuan 610041, China raozh@mail.tsinghua.edu.cn rzhang@sun5.ibp.ac.cn.</nlm:affiliation><country wicri:rule="url">République populaire de Chine</country><wicri:regionArea>Laboratory of Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; National Center for Protein Science Shanghai, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu, Sichuan 610041, China; Collaborative Innovation Center for Biotherapy Chengdu, Sichuan 610041</wicri:regionArea><wicri:noRegion>Sichuan 610041</wicri:noRegion></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Escherichia coli (metabolism)</term><term>Exoribonucleases (chemistry)</term><term>Ligands</term><term>Methyltransferases (chemistry)</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Protein Structure, Secondary</term><term>Protein Structure, Tertiary</term><term>RNA, Messenger (genetics)</term><term>RNA, Viral (genetics)</term><term>SARS Virus (chemistry)</term><term>Sequence Homology, Amino Acid</term><term>Viral Nonstructural Proteins (chemistry)</term><term>Virus Replication (genetics)</term><term>Zinc Fingers</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (génétique)</term><term>ARN viral (génétique)</term><term>Doigts de zinc</term><term>Données de séquences moléculaires</term><term>Escherichia coli (métabolisme)</term><term>Exoribonucleases ()</term><term>Ligands</term><term>Methyltransferases ()</term><term>Modèles moléculaires</term><term>Protéines virales non structurales ()</term><term>Réplication virale (génétique)</term><term>Similitude de séquences d'acides aminés</term><term>Structure secondaire des protéines</term><term>Structure tertiaire des protéines</term><term>Séquence d'acides aminés</term><term>Virus du SRAS ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Exoribonucleases</term><term>Methyltransferases</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Messenger</term><term>RNA, Viral</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN messager</term><term>ARN viral</term><term>Réplication virale</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Escherichia coli</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Escherichia coli</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Ligands</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Protein Structure, Secondary</term><term>Protein Structure, Tertiary</term><term>Sequence Homology, Amino Acid</term><term>Zinc Fingers</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Doigts de zinc</term><term>Données de séquences moléculaires</term><term>Exoribonucleases</term><term>Ligands</term><term>Methyltransferases</term><term>Modèles moléculaires</term><term>Protéines virales non structurales</term><term>Similitude de séquences d'acides aminés</term><term>Structure secondaire des protéines</term><term>Structure tertiaire des protéines</term><term>Séquence d'acides aminés</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Nonstructural protein 14 (nsp14) of coronaviruses (CoV) is important for viral replication and transcription. The N-terminal exoribonuclease (ExoN) domain plays a proofreading role for prevention of lethal mutagenesis, and the C-terminal domain functions as a (guanine-N7) methyl transferase (N7-MTase) for mRNA capping. The molecular basis of both these functions is unknown. Here, we describe crystal structures of severe acute respiratory syndrome (SARS)-CoV nsp14 in complex with its activator nonstructural protein10 (nsp10) and functional ligands. One molecule of nsp10 interacts with ExoN of nsp14 to stabilize it and stimulate its activity. Although the catalytic core of nsp14 ExoN is reminiscent of proofreading exonucleases, the presence of two zinc fingers sets it apart from homologs. Mutagenesis studies indicate that both these zinc fingers are essential for the function of nsp14. We show that a DEEDh (the five catalytic amino acids) motif drives nucleotide excision. The N7-MTase domain exhibits a noncanonical MTase fold with a rare β-sheet insertion and a peripheral zinc finger. The cap-precursor guanosine-P3-adenosine-5',5'-triphosphate and S-adenosyl methionine bind in proximity in a highly constricted pocket between two β-sheets to accomplish methyl transfer. Our studies provide the first glimpses, to our knowledge, into the architecture of the nsp14-nsp10 complex involved in RNA viral proofreading. </div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Ma, Yuanyuan" sort="Ma, Yuanyuan" uniqKey="Ma Y" first="Yuanyuan" last="Ma">Yuanyuan Ma</name></noRegion><name sortKey="Gao, Yan" sort="Gao, Yan" uniqKey="Gao Y" first="Yan" last="Gao">Yan Gao</name><name sortKey="Lou, Zhiyong" sort="Lou, Zhiyong" uniqKey="Lou Z" first="Zhiyong" last="Lou">Zhiyong Lou</name><name sortKey="Rao, Zihe" sort="Rao, Zihe" uniqKey="Rao Z" first="Zihe" last="Rao">Zihe Rao</name><name sortKey="Shaw, Neil" sort="Shaw, Neil" uniqKey="Shaw N" first="Neil" last="Shaw">Neil Shaw</name><name sortKey="Sun, Yuna" sort="Sun, Yuna" uniqKey="Sun Y" first="Yuna" last="Sun">Yuna Sun</name><name sortKey="Wang, Jin" sort="Wang, Jin" uniqKey="Wang J" first="Jin" last="Wang">Jin Wang</name><name sortKey="Wu, Lijie" sort="Wu, Lijie" uniqKey="Wu L" first="Lijie" last="Wu">Lijie Wu</name><name sortKey="Yan, Liming" sort="Yan, Liming" uniqKey="Yan L" first="Liming" last="Yan">Liming Yan</name><name sortKey="Zhang, Rongguang" sort="Zhang, Rongguang" uniqKey="Zhang R" first="Rongguang" last="Zhang">Rongguang Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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