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-Structure paper
タイトル | Structural Basis for Virulence Activation of Francisella tularensis. |
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ジャーナル・号・ページ | Mol Cell, Vol. 81, Issue 1, Page 139-152.e10, Year 2021 |
掲載日 | 2021年1月7日 |
![]() | Brady A Travis / Kathryn M Ramsey / Samantha M Prezioso / Thomas Tallo / Jamie M Wandzilak / Allen Hsu / Mario Borgnia / Alberto Bartesaghi / Simon L Dove / Richard G Brennan / Maria A Schumacher / ![]() |
PubMed 要旨 | 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, ...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. |
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手法 | EM (単粒子) / X線回折 |
解像度 | 2.95 - 4.43 Å |
構造データ | EMDB-21850, PDB-6wmp: EMDB-21851, PDB-6wmr: EMDB-21852, PDB-6wmt: EMDB-21853, PDB-6wmu: ![]() PDB-6weg: |
化合物 | ![]() ChemComp-MG: ![]() ChemComp-G4P: ![]() ChemComp-ZN: |
由来 |
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