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
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