Abstract
The MerR-family transcription factors (TFs) are a large group of bacterial proteins responding to cellular metal ions and multiple antibiotics by binding within central RNA polymerase-binding regions of a promoter. While most TFs alter transcription through protein-protein interactions, MerR TFs are capable of reshaping promoter DNA. To address the question of which mechanism prevails, we determined two cryo-EM structures of transcription activation complexes (TAC) comprising Escherichia coli CueR (a prototype MerR TF), RNAP holoenzyme and promoter DNA. The structures reveal that this TF promotes productive promoter-polymerase association without canonical protein-protein contacts seen between other activator proteins and RNAP. Instead, CueR realigns the key promoter elements in the transcription activation complex by clamp-like protein-DNA interactions: these induce four distinct kinks that ultimately position the -10 element for formation of the transcription bubble. These structural and biochemical results provide strong support for the DNA distortion paradigm of allosteric transcriptional control by MerR TFs.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Allosteric Regulation
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Amino Acid Sequence
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Base Pairing
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Base Sequence
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Binding Sites
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Cryoelectron Microscopy
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DNA, Bacterial / chemistry*
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DNA, Bacterial / genetics
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DNA, Bacterial / metabolism
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Directed RNA Polymerases / chemistry*
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DNA-Directed RNA Polymerases / genetics
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DNA-Directed RNA Polymerases / metabolism
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Escherichia coli / genetics*
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Escherichia coli / metabolism
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Escherichia coli Proteins / chemistry*
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Escherichia coli Proteins / genetics
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Escherichia coli Proteins / metabolism
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Gene Expression Regulation, Bacterial*
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Models, Molecular
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Nucleic Acid Conformation
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Promoter Regions, Genetic
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Protein Binding
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Protein Conformation, alpha-Helical
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Protein Conformation, beta-Strand
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Protein Interaction Domains and Motifs
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Sequence Alignment
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Sequence Homology, Amino Acid
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Trans-Activators / chemistry*
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcriptional Activation
Substances
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Bacterial Proteins
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DNA, Bacterial
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DNA-Binding Proteins
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Escherichia coli Proteins
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MerR protein, Bacteria
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Trans-Activators
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cueR protein, E coli
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DNA-Directed RNA Polymerases