IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28675-0.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28675-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-28675-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Pascal F. Egea & Shu-ou Shan & Johanna Napetschnig & David F. Savage & Peter Walter & Robert M. Stroud, 2004. "Substrate twinning activates the signal recognition particle and its receptor," Nature, Nature, vol. 427(6971), pages 215-221, January.
    2. Guillermo Montoya & Cecilia Svensson & Joen Luirink & Irmgard Sinning, 1997. "Crystal structure of the NG domain from the signal-recognition particle receptor FtsY," Nature, Nature, vol. 385(6614), pages 365-368, January.
    3. Gemma C Atkinson & Tanel Tenson & Vasili Hauryliuk, 2011. "The RelA/SpoT Homolog (RSH) Superfamily: Distribution and Functional Evolution of ppGpp Synthetases and Hydrolases across the Tree of Life," PLOS ONE, Public Library of Science, vol. 6(8), pages 1-21, August.
    4. Alan Brown & Israel S. Fernández & Yuliya Gordiyenko & V. Ramakrishnan, 2016. "Ribosome-dependent activation of stringent control," Nature, Nature, vol. 534(7606), pages 277-280, June.
    5. Mario Halic & Michael Blau & Thomas Becker & Thorsten Mielke & Martin R. Pool & Klemens Wild & Irmgard Sinning & Roland Beckmann, 2006. "Following the signal sequence from ribosomal tunnel exit to signal recognition particle," Nature, Nature, vol. 444(7118), pages 507-511, November.
    6. Ahmad Jomaa & Daniel Boehringer & Marc Leibundgut & Nenad Ban, 2016. "Structures of the E. coli translating ribosome with SRP and its receptor and with the translocon," Nature Communications, Nature, vol. 7(1), pages 1-9, April.
    7. Christoph J. Wienken & Philipp Baaske & Ulrich Rothbauer & Dieter Braun & Stefan Duhr, 2010. "Protein-binding assays in biological liquids using microscale thermophoresis," Nature Communications, Nature, vol. 1(1), pages 1-7, December.
    8. Douglas M. Freymann & Robert J. Keenan & Robert M. Stroud & Peter Walter, 1997. "Structure of the conserved GTPase domain of the signal recognition particle," Nature, Nature, vol. 385(6614), pages 361-364, January.
    9. Mario Halic & Thomas Becker & Martin R. Pool & Christian M. T. Spahn & Robert A. Grassucci & Joachim Frank & Roland Beckmann, 2004. "Structure of the signal recognition particle interacting with the elongation-arrested ribosome," Nature, Nature, vol. 427(6977), pages 808-814, February.
    10. Daniel Sohmen & Shinobu Chiba & Naomi Shimokawa-Chiba & C. Axel Innis & Otto Berninghausen & Roland Beckmann & Koreaki Ito & Daniel N. Wilson, 2015. "Structure of the Bacillus subtilis 70S ribosome reveals the basis for species-specific stalling," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Felix Gersteuer & Martino Morici & Sara Gabrielli & Keigo Fujiwara & Haaris A. Safdari & Helge Paternoga & Lars V. Bock & Shinobu Chiba & Daniel N. Wilson, 2024. "The SecM arrest peptide traps a pre-peptide bond formation state of the ribosome," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Pascal F Egea & Hiro Tsuruta & Gladys P de Leon & Johanna Napetschnig & Peter Walter & Robert M Stroud, 2008. "Structures of the Signal Recognition Particle Receptor from the Archaeon Pyrococcus furiosus: Implications for the Targeting Step at the Membrane," PLOS ONE, Public Library of Science, vol. 3(11), pages 1-14, November.
    3. Jiang Ren & Shuai Wang & Zhi Zong & Ting Pan & Sijia Liu & Wei Mao & Huizhe Huang & Xiaohua Yan & Bing Yang & Xin He & Fangfang Zhou & Long Zhang, 2024. "TRIM28-mediated nucleocapsid protein SUMOylation enhances SARS-CoV-2 virulence," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Naijun Miao & Zhuning Wang & Qinlan Wang & Hongyan Xie & Ninghao Yang & Yanzhe Wang & Jin Wang & Haixia Kang & Wenjuan Bai & Yuanyuan Wang & Rui He & Kepeng Yan & Yang Wang & Qiongyi Hu & Zhaoyuan Liu, 2023. "Oxidized mitochondrial DNA induces gasdermin D oligomerization in systemic lupus erythematosus," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Georg Krainer & Kadi L. Saar & William E. Arter & Timothy J. Welsh & Magdalena A. Czekalska & Raphaël P. B. Jacquat & Quentin Peter & Walther C. Traberg & Arvind Pujari & Akhila K. Jayaram & Pavankuma, 2023. "Direct digital sensing of protein biomarkers in solution," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    6. Cheng Peng & Yuanna Cheng & Mingtong Ma & Qiu Chen & Yongjia Duan & Shanshan Liu & Hongyu Cheng & Hua Yang & Jingping Huang & Wenyi Bu & Chenyue Shi & Xiangyang Wu & Jianxia Chen & Ruijuan Zheng & Zho, 2024. "Mycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    7. Yejinpeng Wang & Lingao Ju & Gang Wang & Kaiyu Qian & Wan Jin & Mingxing Li & Jingtian Yu & Yiliang Shi & Yongzhi Wang & Yi Zhang & Yu Xiao & Xinghuan Wang, 2023. "DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing MYC," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Yuan Lin & Theresa A. Ramelot & Simge Senyuz & Attila Gursoy & Hyunbum Jang & Ruth Nussinov & Ozlem Keskin & Yi Zheng, 2024. "Tumor-derived RHOA mutants interact with effectors in the GDP-bound state," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Martino Morici & Sara Gabrielli & Keigo Fujiwara & Helge Paternoga & Bertrand Beckert & Lars V. Bock & Shinobu Chiba & Daniel N. Wilson, 2024. "RAPP-containing arrest peptides induce translational stalling by short circuiting the ribosomal peptidyltransferase activity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. Manlu Zhu & Xiongfeng Dai, 2023. "Stringent response ensures the timely adaptation of bacterial growth to nutrient downshift," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    11. Simon A. Fromm & Kate M. O’Connor & Michael Purdy & Pramod R. Bhatt & Gary Loughran & John F. Atkins & Ahmad Jomaa & Simone Mattei, 2023. "The translating bacterial ribosome at 1.55 Å resolution generated by cryo-EM imaging services," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    12. Yumin Wang & Boya Gao & Luyuan Zhang & Xudong Wang & Xiaolan Zhu & Haibo Yang & Fengqi Zhang & Xueping Zhu & Badi Zhou & Sean Yao & Aiko Nagayama & Sanghoon Lee & Jian Ouyang & Siang-Boon Koh & Eric L, 2024. "Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Marius A. Klein & Klemens Wild & Miglė Kišonaitė & Irmgard Sinning, 2024. "Methionine aminopeptidase 2 and its autoproteolysis product have different binding sites on the ribosome," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    14. Carlos Barajas & Hsin-Ho Huang & Jesse Gibson & Luis Sandoval & Domitilla Vecchio, 2022. "Feedforward growth rate control mitigates gene activation burden," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    15. Keigo Fujiwara & Naoko Tsuji & Mayu Yoshida & Hiraku Takada & Shinobu Chiba, 2024. "Patchy and widespread distribution of bacterial translation arrest peptides associated with the protein localization machinery," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    16. Noha A. M. Shendy & Melissa Bikowitz & Logan H. Sigua & Yang Zhang & Audrey Mercier & Yousef Khashana & Stephanie Nance & Qi Liu & Ian M. Delahunty & Sarah Robinson & Vanshita Goel & Matthew G. Rees &, 2024. "Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    17. Shuqi Xu & Alice J. Hutchinson & Mahdiar Taheri & Ben Corry & Juan F. Torres, 2024. "Thermodiffusive desalination," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    18. Motohiro Sekiya & Kenta Kainoh & Takehito Sugasawa & Ryunosuke Yoshino & Takatsugu Hirokawa & Hiroaki Tokiwa & Shogo Nakano & Satoru Nagatoishi & Kouhei Tsumoto & Yoshinori Takeuchi & Takafumi Miyamot, 2021. "The transcriptional corepressor CtBP2 serves as a metabolite sensor orchestrating hepatic glucose and lipid homeostasis," Nature Communications, Nature, vol. 12(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28675-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.