7o5b Citations

Inhibition of SRP-dependent protein secretion by the bacterial alarmone (p)ppGpp.

Abstract

The stringent response enables bacteria to respond to nutrient limitation and other stress conditions through production of the nucleotide-based second messengers ppGpp and pppGpp, collectively known as (p)ppGpp. Here, we report that (p)ppGpp inhibits the signal recognition particle (SRP)-dependent protein targeting pathway, which is essential for membrane protein biogenesis and protein secretion. More specifically, (p)ppGpp binds to the SRP GTPases Ffh and FtsY, and inhibits the formation of the SRP receptor-targeting complex, which is central for the coordinated binding of the translating ribosome to the SecYEG translocon. Cryo-EM analysis of SRP bound to translating ribosomes suggests that (p)ppGpp may induce a distinct conformational stabilization of the NG domain of Ffh and FtsY in Bacillus subtilis but not in E. coli.

Reviews citing this publication (4)

  1. Recent advances and perspectives in nucleotide second messenger signaling in bacteria. Hengge R, Pruteanu M, Stülke J, Tschowri N, Turgay K. Microlife 4 uqad015 (2023)
  2. Coping with stress: How bacteria fine-tune protein synthesis and protein transport. Njenga R, Boele J, Öztürk Y, Koch HG. J Biol Chem 299 105163 (2023)
  3. "Metabolic burden" explained: stress symptoms and its related responses induced by (over)expression of (heterologous) proteins in Escherichia coli. Snoeck S, Guidi C, De Mey M. Microb Cell Fact 23 96 (2024)
  4. (p)ppGpp - an important player during heat shock response. Driller K, Cornejo FA, Turgay K. Microlife 4 uqad017 (2023)

Articles citing this publication (7)