Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors
Identifieur interne : 000A88 ( Main/Exploration ); précédent : 000A87; suivant : 000A89Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors
Auteurs : Robert N. Kirchdoerfer ; Andrew B. WardSource :
- Nature Communications [ 2041-1723 ] ; 2019.
Descripteurs français
- KwdFr :
- MESH :
- métabolisme : Virus du SRAS.
- ultrastructure : Coenzymes, Cryomicroscopie électronique, DNA-directed RNA polymerases, Génome viral, Protéines virales non structurales, Virus du SRAS.
English descriptors
- KwdEn :
- MESH :
- chemical , ultrastructure : Coenzymes, DNA-Directed RNA Polymerases, Viral Nonstructural Proteins.
- metabolism : SARS Virus.
- ultrastructure : SARS Virus.
- Cryoelectron Microscopy, Genome, Viral.
Abstract
Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV nsp12 polymerase bound to its essential co-factors, nsp7 and nsp8, using single particle cryo-electron microscopy. nsp12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is bound by two nsp8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into nsp12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.
Url:
DOI: 10.1038/s41467-019-10280-3
PubMed: 31138817
PubMed Central: 6538669
Affiliations:
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Kirchdoerfer</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Ward, Andrew B" sort="Ward, Andrew B" uniqKey="Ward A" first="Andrew B." last="Ward">Andrew B. Ward</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coenzymes (ultrastructure)</term><term>Cryoelectron Microscopy</term><term>DNA-Directed RNA Polymerases (ultrastructure)</term><term>Genome, Viral</term><term>SARS Virus (metabolism)</term><term>SARS Virus (ultrastructure)</term><term>Viral Nonstructural Proteins (ultrastructure)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Coenzymes (ultrastructure)</term><term>Cryomicroscopie électronique</term><term>DNA-directed RNA polymerases (ultrastructure)</term><term>Génome viral</term><term>Protéines virales non structurales (ultrastructure)</term><term>Virus du SRAS (métabolisme)</term><term>Virus du SRAS (ultrastructure)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="ultrastructure" xml:lang="en"><term>Coenzymes</term><term>DNA-Directed RNA Polymerases</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cryoelectron Microscopy</term><term>Genome, Viral</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="fr"><term>Coenzymes</term><term>Cryomicroscopie électronique</term><term>DNA-directed RNA polymerases</term><term>Génome viral</term><term>Protéines virales non structurales</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV nsp12 polymerase bound to its essential co-factors, nsp7 and nsp8, using single particle cryo-electron microscopy. nsp12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is bound by two nsp8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into nsp12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L van der Hoek</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Parry, J" uniqKey="Parry J">J Parry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ge, Xy" uniqKey="Ge X">XY Ge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J Ziebuhr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ahn, Dg" uniqKey="Ahn D">DG Ahn</name></author><author><name sortKey="Choi, Jk" uniqKey="Choi J">JK Choi</name></author><author><name 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Ward</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Punjani, A" uniqKey="Punjani A">A Punjani</name></author><author><name sortKey="Rubinstein, Jl" uniqKey="Rubinstein J">JL Rubinstein</name></author><author><name sortKey="Fleet, Dj" uniqKey="Fleet D">DJ Fleet</name></author><author><name sortKey="Brubaker, Ma" uniqKey="Brubaker M">MA Brubaker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Love, Ra" uniqKey="Love R">RA Love</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emsley, P" uniqKey="Emsley P">P Emsley</name></author><author><name sortKey="Lohkamp, B" uniqKey="Lohkamp B">B Lohkamp</name></author><author><name sortKey="Scott, Wg" uniqKey="Scott W">WG Scott</name></author><author><name sortKey="Cowtan, K" uniqKey="Cowtan K">K Cowtan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dimaio, F" uniqKey="Dimaio F">F 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sort="Kirchdoerfer, Robert N" uniqKey="Kirchdoerfer R" first="Robert N." last="Kirchdoerfer">Robert N. 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