8HIH

Cryo-EM structure of Mycobacterium tuberculosis transcription initiation complex with transcription factor GlnR

This is a non-PDB format compatible entry.

Summary for 8HIH

• Entry DOI: 10.2210/pdb8hih/pdb
• EMDB information: 34816
• Descriptor: DNA-directed RNA polymerase subunit alpha, MAGNESIUM ION, DNA-directed RNA polymerase subunit beta, ... (10 entities in total)
• Functional Keywords: transcription factor, transcription-dna complex, transcription/dna
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 13
• Total formula weight: 638075.72

Authors

Lin, W.,Shi, J.,Xu, J.C. (deposition date: 2022-11-20, release date: 2023-06-07, Last modification date: 2024-07-31)

Primary citation

Shi, J.,Feng, Z.,Xu, J.,Li, F.,Zhang, Y.,Wen, A.,Wang, F.,Song, Q.,Wang, L.,Cui, H.,Tong, S.,Chen, P.,Zhu, Y.,Zhao, G.,Wang, S.,Feng, Y.,Lin, W.
Structural insights into the transcription activation mechanism of the global regulator GlnR from actinobacteria.
Proc.Natl.Acad.Sci.USA, 120:e2300282120-e2300282120, 2023

PubMed Abstract: In actinobacteria, an OmpR/PhoB subfamily protein called GlnR acts as an orphan response regulator and globally coordinates the expression of genes responsible for nitrogen, carbon, and phosphate metabolism in actinobacteria. Although many researchers have attempted to elucidate the mechanisms of GlnR-dependent transcription activation, progress is impeded by lacking of an overall structure of GlnR-dependent transcription activation complex (GlnR-TAC). Here, we report a co-crystal structure of the C-terminal DNA-binding domain of GlnR (GlnR_DBD) in complex with its regulatory -element DNA and a cryo-EM structure of GlnR-TAC which comprises RNA polymerase, GlnR, and a promoter containing four well-characterized conserved GlnR binding sites. These structures illustrate how four GlnR protomers coordinate to engage promoter DNA in a head-to-tail manner, with four N-terminal receiver domains of GlnR (GlnR-RECs) bridging GlnR_DBDs and the RNAP core enzyme. Structural analysis also unravels that GlnR-TAC is stabilized by complex protein-protein interactions between GlnR and the conserved β flap, σR4, αCTD, and αNTD domains of RNAP, which are further confirmed by our biochemical assays. Taken together, these results reveal a global transcription activation mechanism for the master regulator GlnR and other OmpR/PhoB subfamily proteins and present a unique mode of bacterial transcription regulation.

PubMed: 37216560
DOI: 10.1073/pnas.2300282120

Experimental method

ELECTRON MICROSCOPY (3.66 Å)