IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59067-9.html
   My bibliography  Save this article

Proteome-wide determinants of co-translational chaperone binding in bacteria

Author

Listed:
  • Carla Verónica Galmozzi

    (DKFZ-ZMBH Alliance
    Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla
    Universidad de Sevilla)

  • Frank Tippmann

    (DKFZ-ZMBH Alliance)

  • Florian Wruck

    (AMOLF)

  • Josef Johannes Auburger

    (DKFZ-ZMBH Alliance)

  • Ilia Kats

    (DKFZ-ZMBH Alliance
    German Cancer Research Center (DKFZ))

  • Manuel Guennigmann

    (DKFZ-ZMBH Alliance)

  • Katharina Till

    (AMOLF)

  • Edward P. O´Brien

    (University Park)

  • Sander J. Tans

    (AMOLF
    Delft University of Technology)

  • Günter Kramer

    (DKFZ-ZMBH Alliance)

  • Bernd Bukau

    (DKFZ-ZMBH Alliance)

Abstract

Chaperones are essential to the co-translational folding of most proteins. However, the principles of co-translational chaperone interaction throughout the proteome are poorly understood, as current methods are restricted to few substrates and cannot capture nascent protein folding or chaperone binding sites, precluding a comprehensive understanding of productive and erroneous protein biosynthesis. Here, by integrating genome-wide selective ribosome profiling, single-molecule tools, and computational predictions using AlphaFold we show that the binding of the main E. coli chaperones involved in co-translational folding, Trigger Factor (TF) and DnaK correlates with “unsatisfied residues” exposed on nascent partial folds – residues that have begun to form tertiary structure but cannot yet form all native contacts due to ongoing translation. This general principle allows us to predict their co-translational binding across the proteome based on sequence only, which we verify experimentally. The results show that TF and DnaK stably bind partially folded rather than unfolded conformers. They also indicate a synergistic action of TF guiding intra-domain folding and DnaK preventing premature inter-domain contacts, and reveal robustness in the larger chaperone network (TF, DnaK, GroEL). Given the complexity of translation, folding, and chaperone functions, our predictions based on general chaperone binding rules indicate an unexpected underlying simplicity.

Suggested Citation

  • Carla Verónica Galmozzi & Frank Tippmann & Florian Wruck & Josef Johannes Auburger & Ilia Kats & Manuel Guennigmann & Katharina Till & Edward P. O´Brien & Sander J. Tans & Günter Kramer & Bernd Bukau, 2025. "Proteome-wide determinants of co-translational chaperone binding in bacteria," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59067-9
    DOI: 10.1038/s41467-025-59067-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59067-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-025-59067-9?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. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Alireza Mashaghi & Sergey Bezrukavnikov & David P. Minde & Anne S. Wentink & Roman Kityk & Beate Zachmann-Brand & Matthias P. Mayer & Günter Kramer & Bernd Bukau & Sander J. Tans, 2016. "Alternative modes of client binding enable functional plasticity of Hsp70," Nature, Nature, vol. 539(7629), pages 448-451, November.
    3. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    4. Günter Kramer & Thomas Rauch & Wolfgang Rist & Sonja Vorderwülbecke & Holger Patzelt & Agnes Schulze-Specking & Nenad Ban & Elke Deuerling & Bernd Bukau, 2002. "L23 protein functions as a chaperone docking site on the ribosome," Nature, Nature, vol. 419(6903), pages 171-174, September.
    5. Elena Plessa & Lien P. Chu & Sammy H. S. Chan & Oliver L. Thomas & Anaïs M. E. Cassaignau & Christopher A. Waudby & John Christodoulou & Lisa D. Cabrita, 2021. "Nascent chains can form co-translational folding intermediates that promote post-translational folding outcomes in a disease-causing protein," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    6. Nadinath B. Nillegoda & Janine Kirstein & Anna Szlachcic & Mykhaylo Berynskyy & Antonia Stank & Florian Stengel & Kristin Arnsburg & Xuechao Gao & Annika Scior & Ruedi Aebersold & D. Lys Guilbride & R, 2015. "Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation," Nature, Nature, vol. 524(7564), pages 247-251, August.
    7. John B. Ingraham & Max Baranov & Zak Costello & Karl W. Barber & Wujie Wang & Ahmed Ismail & Vincent Frappier & Dana M. Lord & Christopher Ng-Thow-Hing & Erik R. Van Vlack & Shan Tie & Vincent Xue & S, 2023. "Illuminating protein space with a programmable generative model," Nature, Nature, vol. 623(7989), pages 1070-1078, November.
    8. Mian Zhou & Jinhu Guo & Joonseok Cha & Michael Chae & She Chen & Jose M. Barral & Matthew S. Sachs & Yi Liu, 2013. "Non-optimal codon usage affects expression, structure and function of clock protein FRQ," Nature, Nature, vol. 495(7439), pages 111-115, March.
    9. Lars Ferbitz & Timm Maier & Holger Patzelt & Bernd Bukau & Elke Deuerling & Nenad Ban, 2004. "Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins," Nature, Nature, vol. 431(7008), pages 590-596, September.
    10. Chengdong Huang & Paolo Rossi & Tomohide Saio & Charalampos G. Kalodimos, 2016. "Structural basis for the antifolding activity of a molecular chaperone," Nature, Nature, vol. 537(7619), pages 202-206, September.
    11. Christian M. Kaiser & Hung-Chun Chang & Vishwas R. Agashe & Sathish K. Lakshmipathy & Stephanie A. Etchells & Manajit Hayer-Hartl & F. Ulrich Hartl & José M. Barral, 2006. "Real-time observation of trigger factor function on translating ribosomes," Nature, Nature, vol. 444(7118), pages 455-460, November.
    12. Julian O. Streit & Ivana V. Bukvin & Sammy H. S. Chan & Shahzad Bashir & Lauren F. Woodburn & Tomasz Włodarski & Angelo Miguel Figueiredo & Gabija Jurkeviciute & Haneesh K. Sidhu & Charity R. Hornby &, 2024. "The ribosome lowers the entropic penalty of protein folding," Nature, Nature, vol. 633(8028), pages 232-239, September.
    13. Elke Deuerling & Agnes Schulze-Specking & Toshifumi Tomoyasu & Axel Mogk & Bernd Bukau, 1999. "Trigger factor and DnaK cooperate in folding of newly synthesized proteins," Nature, Nature, vol. 400(6745), pages 693-696, August.
    14. Alireza Mashaghi & Günter Kramer & Philipp Bechtluft & Beate Zachmann-Brand & Arnold J. M. Driessen & Bernd Bukau & Sander J. Tans, 2013. "Reshaping of the conformational search of a protein by the chaperone trigger factor," Nature, Nature, vol. 500(7460), pages 98-101, August.
    15. Kevin Wu & Thomas C. Minshull & Sheena E. Radford & Antonio N. Calabrese & James C. A. Bardwell, 2022. "Trigger factor both holds and folds its client proteins," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    16. Thomas Bornemann & Wolf Holtkamp & Wolfgang Wintermeyer, 2014. "Interplay between trigger factor and other protein biogenesis factors on the ribosome," Nature Communications, Nature, vol. 5(1), pages 1-8, September.
    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. Zikun Zhu & Shuai Wang & Shu-ou Shan, 2022. "Ribosome profiling reveals multiple roles of SecA in cotranslational protein export," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Dezerae Cox & Ching-Seng Ang & Nadinath B. Nillegoda & Gavin E. Reid & Danny M. Hatters, 2022. "Hidden information on protein function in censuses of proteome foldedness," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Julian O. Streit & Sammy H. S. Chan & Saifu Daya & John Christodoulou, 2025. "Rational design of 19F NMR labelling sites to probe protein structure and interactions," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    4. Meaghan S. Jankowski & Daniel Griffith & Divya G. Shastry & Jacqueline F. Pelham & Garrett M. Ginell & Joshua Thomas & Pankaj Karande & Alex S. Holehouse & Jennifer M. Hurley, 2024. "Disordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Mary Dayne S. Tai & Lissette Ochoa & Marte I. Flydal & Lorea Velasco-Carneros & Jimena Muntaner & César Santiago & Gloria Gamiz-Arco & Fernando Moro & Kunwar Jung-KC & David Gil-Cantero & Miguel Marci, 2025. "Structural recognition and stabilization of tyrosine hydroxylase by the J-domain protein DNAJC12," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    6. Ramon Duran-Romaña & Bert Houben & Paula Fernández Migens & Ying Zhang & Frederic Rousseau & Joost Schymkowitz, 2025. "Native Fold Delay and its implications for co-translational chaperone binding and protein aggregation," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    7. Fabian Ries & Jasmin Gorlt & Sabrina Kaiser & Vanessa Scherer & Charlotte Seydel & Sandra Nguyen & Andreas Klingl & Julia Legen & Christian Schmitz-Linneweber & Hinrik Plaggenborg & Jediael Z. Y. Ng &, 2025. "A truncated variant of the ribosome-associated trigger factor specifically contributes to plant chloroplast ribosome biogenesis," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    8. Lucien F. Krapp & Fernando A. Meireles & Luciano A. Abriata & Jean Devillard & Sarah Vacle & Maria J. Marcaida & Matteo Dal Peraro, 2024. "Context-aware geometric deep learning for protein sequence design," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    9. Ye Yuan & Lei Chen & Kexu Song & Miaomiao Cheng & Ling Fang & Lingfei Kong & Lanlan Yu & Ruonan Wang & Zhendong Fu & Minmin Sun & Qian Wang & Chengjun Cui & Haojue Wang & Jiuyang He & Xiaonan Wang & Y, 2024. "Stable peptide-assembled nanozyme mimicking dual antifungal actions," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Ivica Odorčić & Mohamed Belal Hamed & Sam Lismont & Lucía Chávez-Gutiérrez & Rouslan G. Efremov, 2024. "Apo and Aβ46-bound γ-secretase structures provide insights into amyloid-β processing by the APH-1B isoform," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    11. Pantelis Livanos & Choy Kriechbaum & Sophia Remers & Arvid Herrmann & Sabine Müller, 2025. "Kinesin-12 POK2 polarization is a prerequisite for a fully functional division site and aids cell plate positioning," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    12. Surabhi Kokane & Ashutosh Gulati & Pascal F. Meier & Rei Matsuoka & Tanadet Pipatpolkai & Giuseppe Albano & Tin Manh Ho & Lucie Delemotte & Daniel Fuster & David Drew, 2025. "PIP2-mediated oligomerization of the endosomal sodium/proton exchanger NHE9," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    13. Stella Vitt & Simone Prinz & Martin Eisinger & Ulrich Ermler & Wolfgang Buckel, 2022. "Purification and structural characterization of the Na+-translocating ferredoxin: NAD+ reductase (Rnf) complex of Clostridium tetanomorphum," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    14. Pierre Azoulay & Joshua Krieger & Abhishek Nagaraj, 2024. "Old Moats for New Models: Openness, Control, and Competition in Generative Artificial Intelligence," NBER Chapters, in: Entrepreneurship and Innovation Policy and the Economy, volume 4, pages 7-46, National Bureau of Economic Research, Inc.
    15. Riya Shah & Thomas C. Panagiotou & Gregory B. Cole & Trevor F. Moraes & Brigitte D. Lavoie & Christopher A. McCulloch & Andrew Wilde, 2024. "The DIAPH3 linker specifies a β-actin network that maintains RhoA and Myosin-II at the cytokinetic furrow," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    16. Yashan Yang & Qianqian Shao & Mingcheng Guo & Lin Han & Xinyue Zhao & Aohan Wang & Xiangyun Li & Bo Wang & Ji-An Pan & Zhenguo Chen & Andrei Fokine & Lei Sun & Qianglin Fang, 2024. "Capsid structure of bacteriophage ΦKZ provides insights into assembly and stabilization of jumbo phages," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    17. Xin Yong & Guowen Jia & Qin Yang & Chunzhuang Zhou & Sitao Zhang & Huaqing Deng & Daniel D. Billadeau & Zhaoming Su & Da Jia, 2025. "Cryo-EM structure of the BLOC-3 complex provides insights into the pathogenesis of Hermansky-Pudlak syndrome," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    18. Bret M. Boyd & Ian James & Kevin P. Johnson & Robert B. Weiss & Sarah E. Bush & Dale H. Clayton & Colin Dale, 2024. "Stochasticity, determinism, and contingency shape genome evolution of endosymbiotic bacteria," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    19. Jun-Yu Si & Yuan-Mei Chen & Ye-Hui Sun & Meng-Xue Gu & Mei-Ling Huang & Lu-Lu Shi & Xiao Yu & Xiao Yang & Qing Xiong & Cheng-Bao Ma & Peng Liu & Zheng-Li Shi & Huan Yan, 2024. "Sarbecovirus RBD indels and specific residues dictating multi-species ACE2 adaptiveness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    20. Deyun Qiu & Jinxin V. Pei & James E. O. Rosling & Vandana Thathy & Dongdi Li & Yi Xue & John D. Tanner & Jocelyn Sietsma Penington & Yi Tong Vincent Aw & Jessica Yi Han Aw & Guoyue Xu & Abhai K. Tripa, 2022. "A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin," Nature Communications, Nature, vol. 13(1), pages 1-18, 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:16:y:2025:i:1:d:10.1038_s41467-025-59067-9. 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.