A G-quadruplex-binding macrodomain within the "SARS-unique domain" is essential for the activity of the SARS-coronavirus replication-transcription complex.
Identifieur interne : 001382 ( Main/Exploration ); précédent : 001381; suivant : 001383A G-quadruplex-binding macrodomain within the "SARS-unique domain" is essential for the activity of the SARS-coronavirus replication-transcription complex.
Auteurs : Yuri Kusov [Allemagne] ; Jinzhi Tan [Allemagne] ; Enrique Alvarez [Espagne] ; Luis Enjuanes [Espagne] ; Rolf Hilgenfeld [Allemagne]Source :
- Virology [ 1096-0341 ] ; 2015.
Descripteurs français
- KwdFr :
- Coloration et marquage, Délétion de séquence, Gènes rapporteurs, Génétique inverse, Luciférases de Renilla (analyse), Luciférases de Renilla (génétique), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), Réplication virale, Structure tertiaire des protéines, Substitution d'acide aminé, Transcription génétique, Virus du SRAS (génétique), Virus du SRAS (physiologie).
- MESH :
- analyse : Luciférases de Renilla.
- génétique : Luciférases de Renilla, Protéines virales non structurales, Virus du SRAS.
- métabolisme : Protéines virales non structurales.
- physiologie : Virus du SRAS.
- Coloration et marquage, Délétion de séquence, Gènes rapporteurs, Génétique inverse, Réplication virale, Structure tertiaire des protéines, Substitution d'acide aminé, Transcription génétique.
English descriptors
- KwdEn :
- Amino Acid Substitution, Genes, Reporter, Luciferases, Renilla (analysis), Luciferases, Renilla (genetics), Protein Structure, Tertiary, Reverse Genetics, SARS Virus (genetics), SARS Virus (physiology), Sequence Deletion, Staining and Labeling, Transcription, Genetic, Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism), Virus Replication.
- MESH :
- chemical , analysis : Luciferases, Renilla.
- chemical , genetics : Luciferases, Renilla, Viral Nonstructural Proteins.
- genetics : SARS Virus.
- chemical , metabolism : Viral Nonstructural Proteins.
- physiology : SARS Virus.
- Amino Acid Substitution, Genes, Reporter, Protein Structure, Tertiary, Reverse Genetics, Sequence Deletion, Staining and Labeling, Transcription, Genetic, Virus Replication.
Abstract
The multi-domain non-structural protein 3 of SARS-coronavirus is a component of the viral replication/transcription complex (RTC). Among other domains, it contains three sequentially arranged macrodomains: the X domain and subdomains SUD-N as well as SUD-M within the "SARS-unique domain". The X domain was proposed to be an ADP-ribose-1"-phosphatase or a poly(ADP-ribose)-binding protein, whereas SUD-NM binds oligo(G)-nucleotides capable of forming G-quadruplexes. Here, we describe the application of a reverse genetic approach to assess the importance of these macrodomains for the activity of the SARS-CoV RTC. To this end, Renilla luciferase-encoding SARS-CoV replicons with selectively deleted macrodomains were constructed and their ability to modulate the RTC activity was examined. While the SUD-N and the X domains were found to be dispensable, the SUD-M domain was crucial for viral genome replication/transcription. Moreover, alanine replacement of charged amino-acid residues of the SUD-M domain, which are likely involved in G-quadruplex-binding, caused abrogation of RTC activity.
DOI: 10.1016/j.virol.2015.06.016
PubMed: 26149721
Affiliations:
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Electronic address: koussov@biochem.uni-luebeck.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany; German Center for Infection Research (DZIF), Hamburg - Lübeck - Borstel Site, University of Lübeck</wicri:regionArea><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Jinzhi" sort="Tan, Jinzhi" uniqKey="Tan J" first="Jinzhi" last="Tan">Jinzhi Tan</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany. Electronic address: tanjinzhi@gmail.com.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck</wicri:regionArea><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Alvarez, Enrique" sort="Alvarez, Enrique" uniqKey="Alvarez E" first="Enrique" last="Alvarez">Enrique Alvarez</name><affiliation wicri:level="3"><nlm:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma, Madrid, Spain. 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Electronic address: hilgenfeld@biochem.uni-luebeck.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany; German Center for Infection Research (DZIF), Hamburg - Lübeck - Borstel Site, University of Lübeck</wicri:regionArea><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion></affiliation></author></analytic><series><title level="j">Virology</title><idno type="eISSN">1096-0341</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 Substitution</term><term>Genes, Reporter</term><term>Luciferases, Renilla (analysis)</term><term>Luciferases, Renilla (genetics)</term><term>Protein Structure, Tertiary</term><term>Reverse Genetics</term><term>SARS Virus (genetics)</term><term>SARS Virus (physiology)</term><term>Sequence Deletion</term><term>Staining and Labeling</term><term>Transcription, Genetic</term><term>Viral Nonstructural Proteins (genetics)</term><term>Viral Nonstructural Proteins (metabolism)</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Coloration et marquage</term><term>Délétion de séquence</term><term>Gènes rapporteurs</term><term>Génétique inverse</term><term>Luciférases de Renilla (analyse)</term><term>Luciférases de Renilla (génétique)</term><term>Protéines virales non structurales (génétique)</term><term>Protéines virales non structurales (métabolisme)</term><term>Réplication virale</term><term>Structure tertiaire des protéines</term><term>Substitution d'acide aminé</term><term>Transcription génétique</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Luciferases, Renilla</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Luciferases, Renilla</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Luciférases de Renilla</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Luciférases de Renilla</term><term>Protéines virales non structurales</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines virales non structurales</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Substitution</term><term>Genes, Reporter</term><term>Protein Structure, Tertiary</term><term>Reverse Genetics</term><term>Sequence Deletion</term><term>Staining and Labeling</term><term>Transcription, Genetic</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Coloration et marquage</term><term>Délétion de séquence</term><term>Gènes rapporteurs</term><term>Génétique inverse</term><term>Réplication virale</term><term>Structure tertiaire des protéines</term><term>Substitution d'acide aminé</term><term>Transcription génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The multi-domain non-structural protein 3 of SARS-coronavirus is a component of the viral replication/transcription complex (RTC). Among other domains, it contains three sequentially arranged macrodomains: the X domain and subdomains SUD-N as well as SUD-M within the "SARS-unique domain". The X domain was proposed to be an ADP-ribose-1"-phosphatase or a poly(ADP-ribose)-binding protein, whereas SUD-NM binds oligo(G)-nucleotides capable of forming G-quadruplexes. Here, we describe the application of a reverse genetic approach to assess the importance of these macrodomains for the activity of the SARS-CoV RTC. To this end, Renilla luciferase-encoding SARS-CoV replicons with selectively deleted macrodomains were constructed and their ability to modulate the RTC activity was examined. While the SUD-N and the X domains were found to be dispensable, the SUD-M domain was crucial for viral genome replication/transcription. Moreover, alanine replacement of charged amino-acid residues of the SUD-M domain, which are likely involved in G-quadruplex-binding, caused abrogation of RTC activity.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Espagne</li></country><region><li>Communauté de Madrid</li></region><settlement><li>Madrid</li></settlement></list><tree><country name="Allemagne"><noRegion><name sortKey="Kusov, Yuri" sort="Kusov, Yuri" uniqKey="Kusov Y" first="Yuri" last="Kusov">Yuri Kusov</name></noRegion><name sortKey="Hilgenfeld, Rolf" sort="Hilgenfeld, Rolf" uniqKey="Hilgenfeld R" first="Rolf" last="Hilgenfeld">Rolf Hilgenfeld</name><name sortKey="Tan, Jinzhi" sort="Tan, Jinzhi" uniqKey="Tan J" first="Jinzhi" last="Tan">Jinzhi Tan</name></country><country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Alvarez, Enrique" sort="Alvarez, Enrique" uniqKey="Alvarez E" first="Enrique" last="Alvarez">Enrique Alvarez</name></region><name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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