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TitleAn alphacoronavirus polymerase structure reveals conserved co-factor functions.
Journal, issue, pagesbioRxiv, Year 2023
Publish dateMar 16, 2023
AuthorsThomas K Anderson / Peter J Hoferle / Kenneth W Lee / Joshua J Coon / Robert N Kirchdoerfer /
PubMed AbstractCoronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral ...Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from the betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine the structure of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. Our structure shows an unexpected nsp8 stoichiometry in comparison to other published coronavirus polymerase structures. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for RNA synthesis for alpha and betacoronaviruses as previously hypothesized. Our work shows the importance of studying diverse coronaviruses to reveal aspects of coronavirus replication while also identifying areas of conservation to be targeted by antiviral drugs.
External linksbioRxiv / PubMed:36993498 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 3.4 Å
Structure data

29779

8g6r

EMDB-29779, PDB-8g6r:
Porcine epidemic diarrhea virus core polymerase complex
Method: EM (single particle) / Resolution: 3.3 Å

42488

8urb

EMDB-42488, PDB-8urb:
Porcine epidemic diarrhea virus complete core polymerase complex
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • porcine epidemic diarrhea virus
  • synthetic construct (others)
KeywordsREPLICATION / Coronavirus / nsp12 / RNA polymerase / PEDV / TRANSFERASE/RNA / TRANSFERASE-RNA complex

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