pH-dependent conformational switch activates the inhibitor of transcription elongation

Oleg Laptenko, Seung Sup Kim, Jookyung Lee, Marina Starodubtseva, Fellipe Cava, Jose Berenguer, Xiang Peng Kong, Sergei Borukhov

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Gfh1, a transcription factor from Thermus thermophilus, inhibits all catalytic activities of RNA polymerase (RNAP). We characterized the Gfh1 structure, function and possible mechanism of action and regulation. Gfh1 inhibits RNAP by competing with NTPs for coordinating the active site Mg 2+ ion. This coordination requires at least two aspartates at the tip of the Gfh1 N-terminal coiled-coil domain (NTD). The overall structure of Gfh1 is similar to that of the Escherichia coli transcript cleavage factor GreA, except for the flipped orientation of the C-terminal domain (CTD). We show that depending on pH, Gfh1-CTD exists in two alternative orientations. At pH above 7, it assumes an inactive 'flipped' orientation seen in the structure, which prevents Gfh1 from binding to RNAP. At lower pH, Gfh1-CTD switches to an active 'Gre-like' orientation, which enables Gfh1 to bind to and inhibit RNAP.

Original languageEnglish (US)
Pages (from-to)2131-2141
Number of pages11
JournalEMBO Journal
Issue number10
StatePublished - May 17 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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