6WMP

F. tularensis RNAPs70-iglA DNA complex

6WMP の概要

• エントリーDOI: 10.2210/pdb6wmp/pdb
• EMDBエントリー: 21850
• 分子名称: DNA-directed RNA polymerase subunit alpha 1, ZINC ION, DNA-directed RNA polymerase subunit alpha 2, ... (10 entities in total)
• 機能のキーワード: rna polymerase complex, transcription
• 由来する生物種: Francisella tularensis subsp. holarctica (strain LVS); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 423380.85

構造登録者

Travis, B.A.,Brennan, R.G.,Schumacher, M.A. (登録日: 2020-04-21, 公開日: 2020-11-11, 最終更新日: 2024-03-06)

主引用文献

Travis, B.A.,Ramsey, K.M.,Prezioso, S.M.,Tallo, T.,Wandzilak, J.M.,Hsu, A.,Borgnia, M.,Bartesaghi, A.,Dove, S.L.,Brennan, R.G.,Schumacher, M.A.
Structural Basis for Virulence Activation of Francisella tularensis.
Mol.Cell, 81:139-, 2021

PubMed Abstract: The bacterium Francisella tularensis (Ft) is one of the most infectious agents known. Ft virulence is controlled by a unique combination of transcription regulators: the MglA-SspA heterodimer, PigR, and the stress signal, ppGpp. MglA-SspA assembles with the σ-associated RNAP holoenzyme (RNAPσ), forming a virulence-specialized polymerase. These factors activate Francisella pathogenicity island (FPI) gene expression, which is required for virulence, but the mechanism is unknown. Here we report FtRNAPσ-promoter-DNA, FtRNAPσ-(MglA-SspA)-promoter DNA, and FtRNAPσ-(MglA-SspA)-ppGpp-PigR-promoter DNA cryo-EM structures. Structural and genetic analyses show MglA-SspA facilitates σ binding to DNA to regulate virulence and virulence-enhancing genes. Our Escherichia coli RNAPσhomodimeric EcSspA structure suggests this is a general SspA-transcription regulation mechanism. Strikingly, our FtRNAPσ-(MglA-SspA)-ppGpp-PigR-DNA structure reveals ppGpp binding to MglA-SspA tethers PigR to promoters. PigR in turn recruits FtRNAP αCTDs to DNA UP elements. Thus, these studies unveil a unique mechanism for Ft pathogenesis involving a virulence-specialized RNAP that employs two (MglA-SspA)-based strategies to activate virulence genes.

PubMed: 33217319
DOI: 10.1016/j.molcel.2020.10.035

実験手法

ELECTRON MICROSCOPY (2.98 Å)