TY  - JOUR
AU  - Galmozzi, Carla Verónica
AU  - Tippmann, Frank
AU  - Wruck, Florian
AU  - Auburger, Josef Johannes
AU  - Kats, Ilia
AU  - Guennigmann, Manuel
AU  - Till, Katharina
AU  - O Brien, Edward P
AU  - Tans, Sander J
AU  - Kramer, Günter
AU  - Bukau, Bernd
TI  - Proteome-wide determinants of co-translational chaperone binding in bacteria.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-00967
SP  - 4361
PY  - 2025
N1  - DKFZ-ZMBH Alliance / #LA:Z999#
AB  - 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.
KW  - Escherichia coli Proteins: metabolism
KW  - Escherichia coli Proteins: genetics
KW  - Escherichia coli Proteins: chemistry
KW  - Proteome: metabolism
KW  - Proteome: genetics
KW  - Escherichia coli: metabolism
KW  - Escherichia coli: genetics
KW  - Protein Folding
KW  - HSP70 Heat-Shock Proteins: metabolism
KW  - HSP70 Heat-Shock Proteins: genetics
KW  - HSP70 Heat-Shock Proteins: chemistry
KW  - Protein Binding
KW  - Molecular Chaperones: metabolism
KW  - Molecular Chaperones: genetics
KW  - Protein Biosynthesis
KW  - Ribosomes: metabolism
KW  - Peptidylprolyl Isomerase: metabolism
KW  - Peptidylprolyl Isomerase: genetics
KW  - Binding Sites
KW  - Escherichia coli Proteins (NLM Chemicals)
KW  - Proteome (NLM Chemicals)
KW  - dnaK protein, E coli (NLM Chemicals)
KW  - trigger factor, E coli (NLM Chemicals)
KW  - HSP70 Heat-Shock Proteins (NLM Chemicals)
KW  - Molecular Chaperones (NLM Chemicals)
KW  - Peptidylprolyl Isomerase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40348781
DO  - DOI:10.1038/s41467-025-59067-9
UR  - https://inrepo02.dkfz.de/record/301282
ER  -