Dissection of two hallmarks of the open promoter complex by mutation in an RNA polymerase core subunit

J Biol Chem. 2000 Aug 18;275(33):25516-22. doi: 10.1074/jbc.M002511200.

Abstract

Deletion of 10 evolutionarily conserved amino acids from the beta subunit of Escherichia coli RNA polymerase leads to a mutant enzyme that is unable to efficiently hold onto DNA. Open promoter complexes formed by the mutant enzyme are in rapid equilibrium with closed complexes and, unlike the wild-type complexes, are highly sensitive to the DNA competitor heparin (Martin, E., Sagitov, V., Burova, E., Nikiforov, V., and Goldfarb, A. (1992) J. Biol. Chem. 267, 20175-20180). Here we show that despite this instability, the mutant enzyme forms partially open complexes at temperatures as low as 0 degrees C when the wild-type complex is fully closed. Thus, the two hallmarks of the open promoter complex, the stability toward a challenge with DNA competitors and the sensitivity toward low temperature, can be uncoupled by mutation and may be independent in the wild-type complex. We use the high resolution structure of Thermus aquaticus RNA polymerase core to build a functional model of promoter complex formation that accounts for the observed defects of the E. coli RNA polymerase mutants.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacillus subtilis / enzymology
  • Catalytic Domain
  • DNA Footprinting
  • DNA-Directed RNA Polymerases / genetics*
  • DNA-Directed RNA Polymerases / metabolism*
  • Enzyme Stability / genetics
  • Escherichia coli / enzymology
  • Gene Deletion
  • Molecular Sequence Data
  • Mutation*
  • Plasmids / metabolism
  • Promoter Regions, Genetic*
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Temperature
  • Thermus / enzymology
  • Transcription, Genetic / genetics

Substances

  • DNA-Directed RNA Polymerases