7ZF2

Protomeric substructure from an octameric assembly of M. tuberculosis RNA polymerase in complex with sigma-b initiation factor

Summary for 7ZF2

• Entry DOI: 10.2210/pdb7zf2/pdb
• Related: 7PP4 7Q4U 7Q59
• EMDB information: 13579 13817 13829 14696 14697
• Descriptor: DNA-directed RNA polymerase subunit alpha, DNA-directed RNA polymerase subunit beta, DNA-directed RNA polymerase subunit beta', ... (7 entities in total)
• Functional Keywords: rna polymerase, self-assembly, octamer, tuberculosis, stress response, hibernation, transcription
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 6
• Total formula weight: 403110.38

Authors

Trapani, S.,Bron, P.,Lai Kee Him, J.,Brodolin, K.,Morichaud, Z.,Vishwakarma, R. (deposition date: 2022-03-31, release date: 2023-02-08, Last modification date: 2024-03-27)

Primary citation

Morichaud, Z.,Trapani, S.,Vishwakarma, R.K.,Chaloin, L.,Lionne, C.,Lai-Kee-Him, J.,Bron, P.,Brodolin, K.
Structural basis of the mycobacterial stress-response RNA polymerase auto-inhibition via oligomerization.
Nat Commun, 14:484-484, 2023

PubMed Abstract: Self-assembly of macromolecules into higher-order symmetric structures is fundamental for the regulation of biological processes. Higher-order symmetric structure self-assembly by the gene expression machinery, such as bacterial DNA-dependent RNA polymerase (RNAP), has never been reported before. Here, we show that the stress-response σ factor from the human pathogen, Mycobacterium tuberculosis, induces the RNAP holoenzyme oligomerization into a supramolecular complex composed of eight RNAP units. Cryo-electron microscopy revealed a pseudo-symmetric structure of the RNAP octamer in which RNAP protomers are captured in an auto-inhibited state and display an open-clamp conformation. The structure shows that σ is sequestered by the RNAP flap and clamp domains. The transcriptional activator RbpA prevented octamer formation by promoting the initiation-competent RNAP conformation. Our results reveal that a non-conserved region of σ is an allosteric controller of transcription initiation and demonstrate how basal transcription factors can regulate gene expression by modulating the RNAP holoenzyme assembly and hibernation.

PubMed: 36717560
DOI: 10.1038/s41467-023-36113-y

Experimental method

ELECTRON MICROSCOPY (3.86 Å)