PmrA, an OmpR/PhoB-family response regulator, triggers gene transcription responsible for polymyxin resistance in bacteria by recognizing promoters where the canonical-35 element is replaced by the pmra-box, representing the PmrA recognition sequence. Here, we report a cryo-electron microscopy (cryo-EM) structure of a bacterial PmrA-dependent transcription activation complex (TAC) containing a PmrA dimer, an RNA polymerase σ70 holoenzyme (RNAPH) and the pbgP promoter DNA. Our structure reveals that the RNAPH mainly contacts the PmrA C-terminal DNA-binding domain (DBD) via electrostatic interactions and reorients the DBD three base pairs upstream of the pmra-box, resulting in a dynamic TAC conformation. In vivo assays show that the substitution of the DNA-recognition residue eliminated its transcriptional activity, while variants with altered RNAPH-interacting residues resulted in enhanced transcriptional activity. Our findings suggest that both PmrA recognition-induced DNA distortion and PmrA promoter escape play crucial roles in its transcriptional activation.
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| http://dx.doi.org/10.1093/nar/gkad724 | DOI Listing |
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