DksA regulates RNA polymerase in Escherichia coli through a network of interactions in the secondary channel that includes Sequence Insertion 1

Andrey Parshin, Anthony L. Shiver, Jookyung Lee, Maria Ozerova, Dina Schneidman-Duhovny, Carol A. Gross, Sergei Borukhov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Sensing and responding to nutritional status is a major challenge for microbial life. In Escherichia coli, the global response to amino acid starvation is orchestrated by guanosine-3′,5′-bisdiphosphate and the transcription factor DksA. DksA alters transcription by binding to RNA polymerase and allosterically modulating its activity. Using genetic analysis, photo-cross-linking, and structural modeling, we show that DksA binds and acts upon RNA polymerase through prominent features of both the nucleotide-access secondary channel and the active-site region. This work is, to our knowledge, the first demonstration of a molecular function for Sequence Insertion 1 in the β subunit of RNA polymerase and significantly advances our understanding of how DksA binds to RNA polymerase and alters transcription.

Original languageEnglish
Pages (from-to)E6862-E6871
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number50
DOIs
StatePublished - 15 Dec 2015
Externally publishedYes

Keywords

  • Lineage-specific insertions
  • Molecular modeling
  • Protein cross-linking
  • Stringent response
  • Transcription regulation

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