Structural basis for dimerization and RNA binding of avian infectious bronchitis virus nsp9.
Identifieur interne : 000D65 ( Main/Exploration ); précédent : 000D64; suivant : 000D66Structural basis for dimerization and RNA binding of avian infectious bronchitis virus nsp9.
Auteurs : Tingting Hu [République populaire de Chine] ; Cheng Chen [République populaire de Chine] ; Huiyan Li [République populaire de Chine] ; Yanshu Dou [République populaire de Chine] ; Ming Zhou [République populaire de Chine] ; Deren Lu [République populaire de Chine] ; Qi Zong [République populaire de Chine] ; Yulei Li [République populaire de Chine] ; Cheng Yang [République populaire de Chine] ; Zhihui Zhong [République populaire de Chine] ; Namit Singh [États-Unis] ; Honggang Hu [République populaire de Chine] ; Rundong Zhang [République populaire de Chine] ; Haitao Yang [République populaire de Chine] ; Dan Su [République populaire de Chine]Source :
- Protein science : a publication of the Protein Society [ 1469-896X ] ; 2017.
Descripteurs français
- KwdFr :
- ARN viral (), ARN viral (métabolisme), Multimérisation de protéines, Protéines de liaison à l'ARN (), Protéines de liaison à l'ARN (métabolisme), Protéines virales (), Protéines virales (métabolisme), Relation structure-activité, Virus de la bronchite infectieuse (), Virus de la bronchite infectieuse (métabolisme).
- MESH :
English descriptors
- KwdEn :
- Infectious bronchitis virus (chemistry), Infectious bronchitis virus (metabolism), Protein Multimerization, RNA, Viral (chemistry), RNA, Viral (metabolism), RNA-Binding Proteins (chemistry), RNA-Binding Proteins (metabolism), Structure-Activity Relationship, Viral Proteins (chemistry), Viral Proteins (metabolism).
- MESH :
- chemical , chemistry : RNA, Viral, RNA-Binding Proteins, Viral Proteins.
- chemistry : Infectious bronchitis virus.
- metabolism : Infectious bronchitis virus, RNA, Viral, RNA-Binding Proteins, Viral Proteins.
- Protein Multimerization, Structure-Activity Relationship.
Abstract
The potential for infection by coronaviruses (CoVs) has become a serious concern with the recent emergence of Middle East respiratory syndrome and severe acute respiratory syndrome (SARS) in the human population. CoVs encode two large polyproteins, which are then processed into 15-16 nonstructural proteins (nsps) that make significant contributions to viral replication and transcription by assembling the RNA replicase complex. Among them, nsp9 plays an essential role in viral replication by forming a homodimer that binds single-stranded RNA. Thus, disrupting nsp9 dimerization is a potential anti-CoV therapy. However, different nsp9 dimer forms have been reported for alpha- and beta-CoVs, and no structural information is available for gamma-CoVs. Here we determined the crystal structure of nsp9 from the avian infectious bronchitis virus (IBV), a representative gamma-CoV that affects the economy of the poultry industry because it can infect domestic fowl. IBV nsp9 forms a homodimer via interactions across a hydrophobic interface, which consists of two parallel alpha helices near the carboxy terminus of the protein. The IBV nsp9 dimer resembles that of SARS-CoV nsp9, indicating that this type of dimerization is conserved among all CoVs. This makes disruption of the dimeric interface an excellent strategy for developing anti-CoV therapies. To facilitate this effort, we characterized the roles of six conserved residues on this interface using site-directed mutagenesis and a multitude of biochemical and biophysical methods. We found that three residues are critical for nsp9 dimerization and its abitlity to bind RNA.
DOI: 10.1002/pro.3150
PubMed: 28257598
Affiliations:
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China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433</wicri:regionArea><wicri:noRegion>200433</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Cheng" sort="Yang, Cheng" uniqKey="Yang C" first="Cheng" last="Yang">Cheng Yang</name><affiliation wicri:level="1"><nlm:affiliation>College of Chemistry, Sichuan University, Chengdu, 610041, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>College of Chemistry, Sichuan University, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author><author><name sortKey="Zhong, Zhihui" sort="Zhong, Zhihui" uniqKey="Zhong Z" first="Zhihui" last="Zhong">Zhihui Zhong</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Non-human Primate Disease Modeling Research, West China Hospital, Sichuan University, Chengdu, 610041, P.R. 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China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433</wicri:regionArea><wicri:noRegion>200433</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Rundong" sort="Zhang, Rundong" uniqKey="Zhang R" first="Rundong" last="Zhang">Rundong Zhang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Haitao" sort="Yang, Haitao" uniqKey="Yang H" first="Haitao" last="Yang">Haitao Yang</name><affiliation wicri:level="1"><nlm:affiliation>School of Life Sciences, Tianjin University, Tianjin, 300072, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>School of Life Sciences, Tianjin University, Tianjin, 300072</wicri:regionArea><wicri:noRegion>300072</wicri:noRegion></affiliation></author><author><name sortKey="Su, Dan" sort="Su, Dan" uniqKey="Su D" first="Dan" last="Su">Dan Su</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. 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China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Cheng" sort="Chen, Cheng" uniqKey="Chen C" first="Cheng" last="Chen">Cheng Chen</name><affiliation wicri:level="1"><nlm:affiliation>School of Life Sciences, Tianjin University, Tianjin, 300072, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>School of Life Sciences, Tianjin University, Tianjin, 300072</wicri:regionArea><wicri:noRegion>300072</wicri:noRegion></affiliation></author><author><name sortKey="Li, Huiyan" sort="Li, Huiyan" uniqKey="Li H" first="Huiyan" last="Li">Huiyan Li</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author><author><name sortKey="Dou, Yanshu" sort="Dou, Yanshu" uniqKey="Dou Y" first="Yanshu" last="Dou">Yanshu Dou</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Ming" sort="Zhou, Ming" uniqKey="Zhou M" first="Ming" last="Zhou">Ming Zhou</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Deren" sort="Lu, Deren" uniqKey="Lu D" first="Deren" last="Lu">Deren Lu</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author><author><name sortKey="Zong, Qi" sort="Zong, Qi" uniqKey="Zong Q" first="Qi" last="Zong">Qi Zong</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yulei" sort="Li, Yulei" uniqKey="Li Y" first="Yulei" last="Li">Yulei Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433</wicri:regionArea><wicri:noRegion>200433</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Cheng" sort="Yang, Cheng" uniqKey="Yang C" first="Cheng" last="Yang">Cheng Yang</name><affiliation wicri:level="1"><nlm:affiliation>College of Chemistry, Sichuan University, Chengdu, 610041, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>College of Chemistry, Sichuan University, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author><author><name sortKey="Zhong, Zhihui" sort="Zhong, Zhihui" uniqKey="Zhong Z" first="Zhihui" last="Zhong">Zhihui Zhong</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Non-human Primate Disease Modeling Research, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Laboratory of Non-human Primate Disease Modeling Research, West China Hospital, Sichuan University, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author><author><name sortKey="Singh, Namit" sort="Singh, Namit" uniqKey="Singh N" first="Namit" last="Singh">Namit Singh</name><affiliation wicri:level="1"><nlm:affiliation>Ludwig Institute for Cancer Research, University of California, La Jolla, San Diego, California, 92093, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Ludwig Institute for Cancer Research, University of California, La Jolla, San Diego, California, 92093</wicri:regionArea><wicri:noRegion>92093</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Honggang" sort="Hu, Honggang" uniqKey="Hu H" first="Honggang" last="Hu">Honggang Hu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433</wicri:regionArea><wicri:noRegion>200433</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Rundong" sort="Zhang, Rundong" uniqKey="Zhang R" first="Rundong" last="Zhang">Rundong Zhang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Haitao" sort="Yang, Haitao" uniqKey="Yang H" first="Haitao" last="Yang">Haitao Yang</name><affiliation wicri:level="1"><nlm:affiliation>School of Life Sciences, Tianjin University, Tianjin, 300072, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>School of Life Sciences, Tianjin University, Tianjin, 300072</wicri:regionArea><wicri:noRegion>300072</wicri:noRegion></affiliation></author><author><name sortKey="Su, Dan" sort="Su, Dan" uniqKey="Su D" first="Dan" last="Su">Dan Su</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041</wicri:regionArea><wicri:noRegion>610041</wicri:noRegion></affiliation></author></analytic><series><title level="j">Protein science : a publication of the Protein Society</title><idno type="eISSN">1469-896X</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Infectious bronchitis virus (chemistry)</term><term>Infectious bronchitis virus (metabolism)</term><term>Protein Multimerization</term><term>RNA, Viral (chemistry)</term><term>RNA, Viral (metabolism)</term><term>RNA-Binding Proteins (chemistry)</term><term>RNA-Binding Proteins (metabolism)</term><term>Structure-Activity Relationship</term><term>Viral Proteins (chemistry)</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral ()</term><term>ARN viral (métabolisme)</term><term>Multimérisation de protéines</term><term>Protéines de liaison à l'ARN ()</term><term>Protéines de liaison à l'ARN (métabolisme)</term><term>Protéines virales ()</term><term>Protéines virales (métabolisme)</term><term>Relation structure-activité</term><term>Virus de la bronchite infectieuse ()</term><term>Virus de la bronchite infectieuse (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>RNA, Viral</term><term>RNA-Binding Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Infectious bronchitis virus</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Infectious bronchitis virus</term><term>RNA, Viral</term><term>RNA-Binding Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN viral</term><term>Protéines de liaison à l'ARN</term><term>Protéines virales</term><term>Virus de la bronchite infectieuse</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Protein Multimerization</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ARN viral</term><term>Multimérisation de protéines</term><term>Protéines de liaison à l'ARN</term><term>Protéines virales</term><term>Relation structure-activité</term><term>Virus de la bronchite infectieuse</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The potential for infection by coronaviruses (CoVs) has become a serious concern with the recent emergence of Middle East respiratory syndrome and severe acute respiratory syndrome (SARS) in the human population. CoVs encode two large polyproteins, which are then processed into 15-16 nonstructural proteins (nsps) that make significant contributions to viral replication and transcription by assembling the RNA replicase complex. Among them, nsp9 plays an essential role in viral replication by forming a homodimer that binds single-stranded RNA. Thus, disrupting nsp9 dimerization is a potential anti-CoV therapy. However, different nsp9 dimer forms have been reported for alpha- and beta-CoVs, and no structural information is available for gamma-CoVs. Here we determined the crystal structure of nsp9 from the avian infectious bronchitis virus (IBV), a representative gamma-CoV that affects the economy of the poultry industry because it can infect domestic fowl. IBV nsp9 forms a homodimer via interactions across a hydrophobic interface, which consists of two parallel alpha helices near the carboxy terminus of the protein. The IBV nsp9 dimer resembles that of SARS-CoV nsp9, indicating that this type of dimerization is conserved among all CoVs. This makes disruption of the dimeric interface an excellent strategy for developing anti-CoV therapies. To facilitate this effort, we characterized the roles of six conserved residues on this interface using site-directed mutagenesis and a multitude of biochemical and biophysical methods. We found that three residues are critical for nsp9 dimerization and its abitlity to bind RNA.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Hu, Tingting" sort="Hu, Tingting" uniqKey="Hu T" first="Tingting" last="Hu">Tingting Hu</name></noRegion><name sortKey="Chen, Cheng" sort="Chen, Cheng" uniqKey="Chen C" first="Cheng" last="Chen">Cheng Chen</name><name sortKey="Dou, Yanshu" sort="Dou, Yanshu" uniqKey="Dou Y" first="Yanshu" last="Dou">Yanshu Dou</name><name sortKey="Hu, Honggang" sort="Hu, Honggang" uniqKey="Hu H" first="Honggang" last="Hu">Honggang Hu</name><name sortKey="Li, Huiyan" sort="Li, Huiyan" uniqKey="Li H" first="Huiyan" last="Li">Huiyan Li</name><name sortKey="Li, Yulei" sort="Li, Yulei" uniqKey="Li Y" first="Yulei" last="Li">Yulei Li</name><name sortKey="Lu, Deren" sort="Lu, Deren" uniqKey="Lu D" first="Deren" last="Lu">Deren Lu</name><name sortKey="Su, Dan" sort="Su, Dan" uniqKey="Su D" first="Dan" last="Su">Dan Su</name><name sortKey="Yang, Cheng" sort="Yang, Cheng" uniqKey="Yang C" first="Cheng" last="Yang">Cheng Yang</name><name sortKey="Yang, Haitao" sort="Yang, Haitao" uniqKey="Yang H" first="Haitao" last="Yang">Haitao Yang</name><name sortKey="Zhang, Rundong" sort="Zhang, Rundong" uniqKey="Zhang R" first="Rundong" last="Zhang">Rundong Zhang</name><name sortKey="Zhong, Zhihui" sort="Zhong, Zhihui" uniqKey="Zhong Z" first="Zhihui" last="Zhong">Zhihui Zhong</name><name sortKey="Zhou, Ming" sort="Zhou, Ming" uniqKey="Zhou M" first="Ming" last="Zhou">Ming Zhou</name><name sortKey="Zong, Qi" sort="Zong, Qi" uniqKey="Zong Q" first="Qi" last="Zong">Qi Zong</name></country><country name="États-Unis"><noRegion><name sortKey="Singh, Namit" sort="Singh, Namit" uniqKey="Singh N" first="Namit" last="Singh">Namit Singh</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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