7KIM
Mycobacterium tuberculosis WT RNAP transcription closed promoter complex with WhiB7 transcription factor
Summary for 7KIM
Entry DOI | 10.2210/pdb7kim/pdb |
EMDB information | 22887 |
Descriptor | DNA-directed RNA polymerase subunit alpha, Probable transcriptional regulator WhiB7, ZINC ION, ... (13 entities in total) |
Functional Keywords | rna polymerase, transcription factor, mycobacterium tuberculosis, iron cluster, transcription, transferase-dna complex, transferase/dna |
Biological source | Mycobacterium tuberculosis More |
Total number of polymer chains | 11 |
Total formula weight | 524918.91 |
Authors | Lilic, M.,Darst, S.A.,Campbell, E.A. (deposition date: 2020-10-23, release date: 2021-04-21, Last modification date: 2025-05-28) |
Primary citation | Lilic, M.,Darst, S.A.,Campbell, E.A. Structural basis of transcriptional activation by the Mycobacterium tuberculosis intrinsic antibiotic-resistance transcription factor WhiB7. Mol.Cell, 81:2875-2886.e5, 2021 Cited by PubMed Abstract: In pathogenic mycobacteria, transcriptional responses to antibiotics result in induced antibiotic resistance. WhiB7 belongs to the Actinobacteria-specific family of Fe-S-containing transcription factors and plays a crucial role in inducible antibiotic resistance in mycobacteria. Here, we present cryoelectron microscopy structures of Mycobacterium tuberculosis transcriptional regulatory complexes comprising RNA polymerase σ-holoenzyme, global regulators CarD and RbpA, and WhiB7, bound to a WhiB7-regulated promoter. The structures reveal how WhiB7 interacts with σ-holoenzyme while simultaneously interacting with an AT-rich sequence element via its AT-hook. Evidently, AT-hooks, rare elements in bacteria yet prevalent in eukaryotes, bind to target AT-rich DNA sequences similarly to the nuclear chromosome binding proteins. Unexpectedly, a subset of particles contained a WhiB7-stabilized closed promoter complex, revealing this intermediate's structure, and we apply kinetic modeling and biochemical assays to rationalize how WhiB7 activates transcription. Altogether, our work presents a comprehensive view of how WhiB7 serves to activate gene expression leading to antibiotic resistance. PubMed: 34171296DOI: 10.1016/j.molcel.2021.05.017 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.38 Å) |
Structure validation
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