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Structural basis of RNA polymerase inhibition by viral and host factors

DOI: 10.1038/s41467-021-25666-5 DOI Help

Authors: Simona Pilotto (University College London) , Thomas Fouqueau (University College London) , Natalya Lukoyanova (Birkbeck College, London) , Carol Sheppard (Imperial College London) , Soizick Lucas-Staat (Institut Pasteur) , Luis Miguel Diaz-Santin (Birkbeck College, London) , Dorota Matelska (University College London) , David Prangishvili (vane Javakhishvili Tbilisi State University) , Alan C. M. Cheung (University of Bristol) , Finn Werner (University College London (UCL))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 12

State: Published (Approved)
Published: September 2021
Diamond Proposal Number(s): 20287

Open Access Open Access

Abstract: 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.

Journal Keywords: Archaeal biology; Cryoelectron microscopy; Structural biology; Virus–host interactions

Diamond Keywords: Viruses

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios III-Titan Krios III at Diamond , Krios IV-Titan Krios IV at Diamond

Added On: 21/09/2021 14:07


Discipline Tags:

Life Sciences & Biotech Structural biology

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)