Regulation of (p)ppGpp hydrolysis by a conserved archetypal regulatory domain

Nucleic Acids Res. 2019 Jan 25;47(2):843-854. doi: 10.1093/nar/gky1201.

Abstract

Sensory and regulatory domains allow bacteria to adequately respond to environmental changes. The regulatory ACT (Aspartokinase, Chorismate mutase and TyrA) domains are mainly found in metabolic-related proteins as well as in long (p)ppGpp synthetase/hydrolase enzymes. Here, we investigate the functional role of the ACT domain of SpoT, the only (p)ppGpp synthetase/hydrolase of Caulobacter crescentus. We show that SpoT requires the ACT domain to efficiently hydrolyze (p)ppGpp. In addition, our in vivo and in vitro data show that the phosphorylated version of EIIANtr (EIIANtr∼P) interacts directly with the ACT and inhibits the hydrolase activity of SpoT. Finally, we highlight the conservation of the ACT-dependent interaction between EIIANtr∼P and SpoT/Rel along with the phosphotransferase system (PTSNtr)-dependent regulation of (p)ppGpp accumulation upon nitrogen starvation in Sinorhizobium meliloti, a plant-associated α-proteobacterium. Thus, this work suggests that α-proteobacteria might have inherited from a common ancestor, a PTSNtr dedicated to modulate (p)ppGpp levels in response to nitrogen availability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism
  • Caulobacter crescentus / enzymology*
  • Guanosine Pentaphosphate / metabolism*
  • Hydrolases / chemistry
  • Hydrolases / metabolism
  • Hydrolysis
  • Ligases / chemistry*
  • Ligases / metabolism*
  • Protein Domains
  • Protein Interaction Domains and Motifs
  • Sinorhizobium meliloti / metabolism

Substances

  • Bacterial Proteins
  • Guanosine Pentaphosphate
  • Hydrolases
  • Ligases
  • guanosine 3',5'-polyphosphate synthetases