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Structure paper

TitleStructural basis of RNA polymerase inhibition by viral and host factors.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 5523, Year 2021
Publish dateSep 17, 2021
AuthorsSimona Pilotto / Thomas Fouqueau / Natalya Lukoyanova / Carol Sheppard / Soizick Lucas-Staat / Luis Miguel Díaz-Santín / Dorota Matelska / David Prangishvili / Alan C M Cheung / Finn Werner /
PubMed AbstractRNA polymerase inhibition plays an important role in the regulation of transcription in response to environmental changes and in the virus-host relationship. Here we present the high-resolution ...RNA polymerase inhibition plays an important role in the regulation of transcription in response to environmental changes and in the virus-host relationship. Here we present the high-resolution structures of two such RNAP-inhibitor complexes that provide the structural bases underlying RNAP inhibition in archaea. The Acidianus two-tailed virus encodes the RIP factor that binds inside the DNA-binding channel of RNAP, inhibiting transcription by occlusion of binding sites for nucleic acid and the transcription initiation factor TFB. Infection with the Sulfolobus Turreted Icosahedral Virus induces the expression of the host factor TFS4, which binds in the RNAP funnel similarly to eukaryotic transcript cleavage factors. However, TFS4 allosterically induces a widening of the DNA-binding channel which disrupts trigger loop and bridge helix motifs. Importantly, the conformational changes induced by TFS4 are closely related to inactivated states of RNAP in other domains of life indicating a deep evolutionary conservation of allosteric RNAP inhibition.
External linksNat Commun / PubMed:34535646 / PubMed Central
MethodsEM (single particle)
Resolution2.61 - 3.27 Å
Structure data

EMDB-12960, PDB-7ok0:
Cryo-EM structure of the Sulfolobus acidocaldarius RNA polymerase at 2.88 A
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-13026, PDB-7oq4:
Cryo-EM structure of the ATV RNAP Inhibitory Protein (RIP) bound to the DNA-binding channel of the host's RNA polymerase
Method: EM (single particle) / Resolution: 3.27 Å

EMDB-13034, PDB-7oqy:
Cryo-EM structure of the cellular negative regulator TFS4 bound to the archaeal RNA polymerase
Method: EM (single particle) / Resolution: 2.61 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-F3S:
FE3-S4 CLUSTER / Iron–sulfur cluster

Source
  • sulfolobus acidocaldarius (strain atcc 33909 / dsm 639 / jcm 8929 / nbrc 15157 / ncimb 11770) (acidophilic)
  • sulfolobus acidocaldarius dsm 639 (acidophilic)
  • acidianus two-tailed virus
  • saccharolobus solfataricus (strain atcc 35092 / dsm 1617 / jcm 11322 / p2) (archaea)
KeywordsTRANSCRIPTION / RNA polymerase / Archaea / Crenarchaea / VIRAL PROTEIN / viral inhibitor / transcription inhibition / ATV / archaeal virus / negative regulator / inhibitor / Sso TFS4 / trancript cleavage factor

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