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082 _ _ |a 500
100 1 _ |a Galmozzi, Carla Verónica
|b 0
245 _ _ |a Proteome-wide determinants of co-translational chaperone binding in bacteria.
260 _ _ |a [London]
|c 2025
|b Springer Nature
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520 _ _ |a 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.
536 _ _ |a 312 - Funktionelle und strukturelle Genomforschung (POF4-312)
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650 _ 7 |a Escherichia coli Proteins
|2 NLM Chemicals
650 _ 7 |a Proteome
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650 _ 7 |a dnaK protein, E coli
|0 EC 3.6.1.-
|2 NLM Chemicals
650 _ 7 |a trigger factor, E coli
|0 EC 5.2.1.-
|2 NLM Chemicals
650 _ 7 |a HSP70 Heat-Shock Proteins
|2 NLM Chemicals
650 _ 7 |a Molecular Chaperones
|2 NLM Chemicals
650 _ 7 |a Peptidylprolyl Isomerase
|0 EC 5.2.1.8
|2 NLM Chemicals
650 _ 2 |a Escherichia coli Proteins: metabolism
|2 MeSH
650 _ 2 |a Escherichia coli Proteins: genetics
|2 MeSH
650 _ 2 |a Escherichia coli Proteins: chemistry
|2 MeSH
650 _ 2 |a Proteome: metabolism
|2 MeSH
650 _ 2 |a Proteome: genetics
|2 MeSH
650 _ 2 |a Escherichia coli: metabolism
|2 MeSH
650 _ 2 |a Escherichia coli: genetics
|2 MeSH
650 _ 2 |a Protein Folding
|2 MeSH
650 _ 2 |a HSP70 Heat-Shock Proteins: metabolism
|2 MeSH
650 _ 2 |a HSP70 Heat-Shock Proteins: genetics
|2 MeSH
650 _ 2 |a HSP70 Heat-Shock Proteins: chemistry
|2 MeSH
650 _ 2 |a Protein Binding
|2 MeSH
650 _ 2 |a Molecular Chaperones: metabolism
|2 MeSH
650 _ 2 |a Molecular Chaperones: genetics
|2 MeSH
650 _ 2 |a Protein Biosynthesis
|2 MeSH
650 _ 2 |a Ribosomes: metabolism
|2 MeSH
650 _ 2 |a Peptidylprolyl Isomerase: metabolism
|2 MeSH
650 _ 2 |a Peptidylprolyl Isomerase: genetics
|2 MeSH
650 _ 2 |a Binding Sites
|2 MeSH
700 1 _ |a Tippmann, Frank
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700 1 _ |a Wruck, Florian
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700 1 _ |a Auburger, Josef Johannes
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700 1 _ |a Kats, Ilia
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700 1 _ |a Guennigmann, Manuel
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700 1 _ |a Till, Katharina
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700 1 _ |a O Brien, Edward P
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700 1 _ |a Tans, Sander J
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700 1 _ |a Kramer, Günter
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700 1 _ |a Bukau, Bernd
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773 _ _ |a 10.1038/s41467-025-59067-9
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