Positive allosteric feedback regulation of the stringent response enzyme RelA by its product

EMBO Rep. 2012 Sep;13(9):835-9. doi: 10.1038/embor.2012.106. Epub 2012 Jul 20.


During the stringent response, Escherichia coli enzyme RelA produces the ppGpp alarmone, which in turn regulates transcription, translation and replication. We show that ppGpp dramatically increases the turnover rate of its own ribosome-dependent synthesis by RelA, resulting in direct positive regulation of an enzyme by its product. Positive allosteric regulation therefore constitutes a new mechanism of enzyme activation. By integrating the output of individual RelA molecules and ppGpp degradation pathways, this regulatory circuit contributes to a fast and coordinated transition to stringency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Enzyme Activation
  • Escherichia coli / enzymology*
  • Escherichia coli / metabolism
  • Guanosine Tetraphosphate / biosynthesis*
  • Ligases / metabolism*
  • Ribosomes / metabolism


  • Guanosine Tetraphosphate
  • Ligases
  • guanosine 3',5'-polyphosphate synthetases