6WEG

Structure of Ft (MglA-SspA)-ppGpp-PigR peptide complex

Summary for 6WEG

• Entry DOI: 10.2210/pdb6weg/pdb
• Descriptor: Stringent starvation protein A, regulator of transcription, MglA, Peptide, ... (5 entities in total)
• Functional Keywords: francisella tularensis, bioweapon, mgla-sspa, pigr, ppgpp, transcription
• Biological source: Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4); More
• Total number of polymer chains: 5
• Total formula weight: 99327.37

Authors

Schumacher, M.A.,Brennan, R. (deposition date: 2020-04-02, release date: 2020-11-11, Last modification date: 2023-10-18)

Primary citation

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, 81:139-152.e10, 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

Experimental method

X-RAY DIFFRACTION (2.95 Å)