Structural basis for transcription initiation by bacterial ECF σ factors.

Li, Lingting; Fang, Chengli; Zhuang, Ningning; Wang, Tiantian; Zhang, Yu · Nat Commun · 2019

basic_science · Level V

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Abstract

Bacterial RNA polymerase employs extra-cytoplasmic function (ECF) σ factors to regulate context-specific gene expression programs. Despite being the most abundant and divergent σ factor class, the structural basis of ECF σ factor-mediated transcription initiation remains unknown. Here, we determine a crystal structure of Mycobacterium tuberculosis (Mtb) RNAP holoenzyme comprising an RNAP core enzyme and the ECF σ factor σ<sup>H</sup> (σ<sup>H</sup>-RNAP) at 2.7 Å, and solve another crystal structure of a transcription initiation complex of Mtb σ<sup>H</sup>-RNAP (σ<sup>H</sup>-RPo) comprising promoter DNA and an RNA primer at 2.8 Å. The two structures together reveal the interactions between σ<sup>H</sup> and RNAP that are essential for σ<sup>H</sup>-RNAP holoenzyme assembly as well as the interactions between σ<sup>H</sup>-RNAP and promoter DNA responsible for stringent promoter recognition and for promoter unwinding. Our study establishes that ECF σ factors and primary σ factors employ distinct mechanisms for promoter recognition and for promoter unwinding.

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