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Cryo-EM structure of Mycobacterium tuberculosis transcription initiation complex with transcription factor GlnRCryo-EM structure of Mycobacterium tuberculosis transcription initiation complex with transcription factor GlnR
Structural highlights
FunctionRPOA_MYCTU DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_00059][1] Publication Abstract from PubMedIn 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 beta flap, sigma(A)R4, alphaCTD, and alphaNTD 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. Structural insights into the transcription activation mechanism of the global regulator GlnR from actinobacteria.,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 Proc Natl Acad Sci U S A. 2023 May 30;120(22):e2300282120. doi: , 10.1073/pnas.2300282120. Epub 2023 May 22. PMID:37216560[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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