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

Czech, Laura; Mais, Christopher-Nils; Kratzat, Hanna; Sarmah, Pinku; Giammarinaro, Pietro; Freibert, Sven-Andreas; Esser, Hanna Folke; Musial, Joanna; Berninghausen, Otto; Steinchen, Wieland; Beckmann, Roland; Koch, Hans-Georg und Bange, Gert (2022): Inhibition of SRP-dependent protein secretion by the bacterial alarmone (p)ppGpp. In: Nature Communications, Bd. 13, Nr. 1, 1069

Abstract

Bacterial responses to nutrient limitation and other stress conditions are often modulated by the nucleotide-based second messenger (p)ppGpp. Here, the authors show that (p)ppGpp inhibits the SRP membrane-protein insertion and secretion pathway by binding to GTPases Ffh and FtsY. 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Biochemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 403222702
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 278002225