Summary information and primary citation

PDB-id
8hih; SNAP-derived features in text and JSON formats; DNAproDB
Class
transcription-DNA
Method
cryo-EM (3.66 Å)
Summary
cryo-EM structure of mycobacterium tuberculosis transcription initiation complex with transcription factor glnr
Reference
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 (2023): "Structural insights into the transcription activation mechanism of the global regulator GlnR from actinobacteria." Proc.Natl.Acad.Sci.USA, 120, e2300282120. doi: 10.1073/pnas.2300282120.
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 cis-element DNA and a cryo-EM structure of GlnR-TAC which comprises Mycobacterium tuberculosis 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, σAR4, 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.

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