Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2019 |
---|---|
Erschienen: |
2019 |
Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
---|---|
Enthalten in: |
Nature communications - 10(2019), 1 vom: 28. Mai, Seite 2342 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Kirchdoerfer, Robert N [VerfasserIn] |
---|
Links: |
---|
Themen: |
Coenzymes |
---|
Anmerkungen: |
Date Completed 17.06.2019 Date Revised 11.02.2024 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.1038/s41467-019-10280-3 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM297567381 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM297567381 | ||
003 | DE-627 | ||
005 | 20240211231823.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2019 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1038/s41467-019-10280-3 |2 doi | |
028 | 5 | 2 | |a pubmed24n1288.xml |
035 | |a (DE-627)NLM297567381 | ||
035 | |a (NLM)31138817 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Kirchdoerfer, Robert N |e verfasserin |4 aut | |
245 | 1 | 0 | |a Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors |
264 | 1 | |c 2019 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 17.06.2019 | ||
500 | |a Date Revised 11.02.2024 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Coenzymes |2 NLM | |
650 | 7 | |a Viral Nonstructural Proteins |2 NLM | |
650 | 7 | |a DNA-Directed RNA Polymerases |2 NLM | |
650 | 7 | |a EC 2.7.7.6 |2 NLM | |
700 | 1 | |a Ward, Andrew B |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 10(2019), 1 vom: 28. Mai, Seite 2342 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
773 | 1 | 8 | |g volume:10 |g year:2019 |g number:1 |g day:28 |g month:05 |g pages:2342 |
856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-019-10280-3 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 10 |j 2019 |e 1 |b 28 |c 05 |h 2342 |