Structural basis of RNA polymerase inhibition by viral and host factors

Autor: Thomas Fouqueau, David Prangishvili, Finn Werner, Dorota Matelska, Natalya Lukoyanova, Luis Miguel Díaz-Santín, Alan C. M. Cheung, Simona Pilotto, Soizick Lucas-Staat, Carol Sheppard
Přispěvatelé: University College of London [London] (UCL), Birkbeck College [University of London], Imperial College London, Département de Microbiologie - Department of Microbiology, Institut Pasteur [Paris], Ivane Javakhishvili Tbilisi State University (TSU), University of Bristol [Bristol], Research in the RNAP laboratory at UCL is funded by a Wellcome Investigator Award in Science to FW (WT 207446/Z/17/Z) with the title Mechanisms and Regulation of RNAP transcription., Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)
Rok vydání: 2021
Předmět:
Models
Molecular
Cleavage factor
Time Factors
Archaeal Proteins
Science
[SDV]Life Sciences [q-bio]
genetic processes
Allosteric regulation
General Physics and Astronomy
Virus-host interactions
Article
Protein Structure
Secondary
General Biochemistry
Genetics and Molecular Biology
Viral Proteins
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Allosteric Regulation
Transcription (biology)
RNA polymerase
Amino Acid Sequence
Binding site
030304 developmental biology
Host factor
0303 health sciences
Multidisciplinary
biology
Chemistry
Cryoelectron Microscopy
DNA
DNA-Directed RNA Polymerases
General Chemistry
biology.organism_classification
Viroids
3. Good health
Cell biology
Sulfolobus
enzymes and coenzymes (carbohydrates)
Viruses
health occupations
Nucleic acid
bacteria
Structural biology
Archaeal biology
030217 neurology & neurosurgery
Protein Binding
Zdroj: Nature Communications
Nature Communications, Nature Publishing Group, 2021, 12 (1), pp.5523. ⟨10.1038/s41467-021-25666-5⟩
Nature Communications, 2021, 12 (1), pp.5523. ⟨10.1038/s41467-021-25666-5⟩
Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021)
ISSN: 2041-1723
DOI: 10.1038/s41467-021-25666-5
Popis: 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.
Understanding the structural basis for the inhibition of archaeal eukaryotic-like RNA polymerases (RNAPs) during virus infection is of interest for drug design. Here, the authors present the cryo-EM structures of apo Sulfolobus acidocaldarius RNAP and the RNAP complex structures with two regulatory factors, RIP and TFS4 that inhibit transcription and discuss their inhibitory mechanisms.
Databáze: OpenAIRE
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