Structural visualization of transcription activated by a multidrug-sensing MerR family regulator.

Publication Type:

Journal Article

Source:

Nat Commun, Volume 12, Issue 1, p.2702 (2021)

Keywords:

Amino Acid Motifs, Bacterial Proteins, Base Sequence, Binding Sites, Cloning, Molecular, Cryoelectron Microscopy, Crystallography, X-Ray, DNA, Bacterial, DNA-Binding Proteins, DNA-Directed RNA Polymerases, Escherichia coli, Gene Expression, Gene Expression Regulation, Bacterial, Genetic Vectors, Models, Molecular, Nucleic Acid Conformation, Promoter Regions, Genetic, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Recombinant Proteins, Transcription Elongation, Genetic, Transcription Initiation, Genetic

Abstract:

<p>Bacterial RNA polymerase (RNAP) holoenzyme initiates transcription by recognizing the conserved -35 and -10 promoter elements that are optimally separated by a 17-bp spacer. The MerR family of transcriptional regulators activate suboptimal 19-20&thinsp;bp spacer promoters in response to myriad cellular signals, ranging from heavy metals to drug-like compounds. The regulation of transcription by MerR family regulators is not fully understood. Here we report one crystal structure of a multidrug-sensing MerR family regulator EcmrR and nine cryo-electron microscopy structures that capture the EcmrR-dependent transcription process from promoter opening to initial transcription to RNA elongation. These structures reveal that EcmrR is a dual ligand-binding factor that reshapes the suboptimal 19-bp spacer DNA to enable optimal promoter recognition, sustains promoter remodeling to stabilize initial transcribing complexes, and finally dissociates from the promoter to reverse DNA remodeling and facilitate the transition to elongation. Our findings yield a comprehensive model for transcription regulation by MerR family factors and provide insights into the transition from transcription initiation to elongation.</p>

PDB: 
6WL5
Detector: 
PILATUS
Beamline: 
24-ID-C