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

Author

Listed:
  • Laura Czech

    (Center for Synthetic Microbiology (SYNMIKRO) and Department of Chemistry Philipps-Universität Marburg)

  • Christopher-Nils Mais

    (Center for Synthetic Microbiology (SYNMIKRO) and Department of Chemistry Philipps-Universität Marburg)

  • Hanna Kratzat

    (Ludwig-Maximilians-Universität, LMU)

  • Pinku Sarmah

    (Albert-Ludwigs-Universität Freiburg
    Albert-Ludwigs-Universität Freiburg)

  • Pietro Giammarinaro

    (Center for Synthetic Microbiology (SYNMIKRO) and Department of Chemistry Philipps-Universität Marburg)

  • Sven-Andreas Freibert

    (Philipps-Universität Marburg
    Philipps-Universität Marburg)

  • Hanna Folke Esser

    (Ludwig-Maximilians-Universität, LMU)

  • Joanna Musial

    (Ludwig-Maximilians-Universität, LMU)

  • Otto Berninghausen

    (Ludwig-Maximilians-Universität, LMU)

  • Wieland Steinchen

    (Center for Synthetic Microbiology (SYNMIKRO) and Department of Chemistry Philipps-Universität Marburg)

  • Roland Beckmann

    (Ludwig-Maximilians-Universität, LMU)

  • Hans-Georg Koch

    (Albert-Ludwigs-Universität Freiburg)

  • Gert Bange

    (Center for Synthetic Microbiology (SYNMIKRO) and Department of Chemistry Philipps-Universität Marburg
    Max-Planck Institute for terrestrial Microbiology)

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.

Suggested Citation

  • Laura Czech & Christopher-Nils Mais & Hanna Kratzat & Pinku Sarmah & Pietro Giammarinaro & Sven-Andreas Freibert & Hanna Folke Esser & Joanna Musial & Otto Berninghausen & Wieland Steinchen & Roland B, 2022. "Inhibition of SRP-dependent protein secretion by the bacterial alarmone (p)ppGpp," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28675-0
    DOI: 10.1038/s41467-022-28675-0
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    References listed on IDEAS

    as
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