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@ARTICLE{Galmozzi:301282,
author = {C. V. Galmozzi and F. Tippmann and F. Wruck and J. J.
Auburger and I. Kats$^*$ and M. Guennigmann and K. Till and
E. P. O Brien and S. J. Tans and G. Kramer and B. Bukau$^*$},
title = {{P}roteome-wide determinants of co-translational chaperone
binding in bacteria.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-00967},
pages = {4361},
year = {2025},
note = {DKFZ-ZMBH Alliance / #LA:Z999#},
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.},
keywords = {Escherichia coli Proteins: metabolism / Escherichia coli
Proteins: genetics / Escherichia coli Proteins: chemistry /
Proteome: metabolism / Proteome: genetics / Escherichia
coli: metabolism / Escherichia coli: genetics / Protein
Folding / HSP70 Heat-Shock Proteins: metabolism / HSP70
Heat-Shock Proteins: genetics / HSP70 Heat-Shock Proteins:
chemistry / Protein Binding / Molecular Chaperones:
metabolism / Molecular Chaperones: genetics / Protein
Biosynthesis / Ribosomes: metabolism / Peptidylprolyl
Isomerase: metabolism / Peptidylprolyl Isomerase: genetics /
Binding Sites / Escherichia coli Proteins (NLM Chemicals) /
Proteome (NLM Chemicals) / dnaK protein, E coli (NLM
Chemicals) / trigger factor, E coli (NLM Chemicals) / HSP70
Heat-Shock Proteins (NLM Chemicals) / Molecular Chaperones
(NLM Chemicals) / Peptidylprolyl Isomerase (NLM Chemicals)},
cin = {B260},
ddc = {500},
cid = {I:(DE-He78)B260-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40348781},
doi = {10.1038/s41467-025-59067-9},
url = {https://inrepo02.dkfz.de/record/301282},
}