7KIF

Mycobacterium tuberculosis WT RNAP transcription open promoter complex with WhiB7 transcription factor

7KIF の概要

• エントリーDOI: 10.2210/pdb7kif/pdb
• EMDBエントリー: 22886
• 分子名称: DNA-directed RNA polymerase subunit alpha, Probable transcriptional regulator WhiB7, ZINC ION, ... (13 entities in total)
• 機能のキーワード: rna polymerase, transcription factor, mycobacterium tuberculosis, iron cluster, transcription, transferase-dna complex, transferase/dna
• 由来する生物種: Mycobacterium tuberculosis; 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 524918.91

構造登録者

Lilic, M.,Darst, S.A.,Campbell, E.A. (登録日: 2020-10-23, 公開日: 2021-04-21, 最終更新日: 2025-05-14)

主引用文献

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

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: 34171296
DOI: 10.1016/j.molcel.2021.05.017

実験手法

ELECTRON MICROSCOPY (2.94 Å)