TY  - JOUR
AU  - Till, Katharina
AU  - Seinen, Anne-Bart
AU  - Wruck, Florian
AU  - Sunderlikova, Vanda
AU  - Galmozzi, Carla
AU  - Katranidis, Alexandros
AU  - Bukau, Bernd
AU  - Kramer, Günter
AU  - Tans, Sander J
TI  - Trigger factor accelerates nascent chain compaction and folding.
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 122
IS  - 30
SN  - 0027-8424
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - DKFZ-2025-01544
SP  - e2422678122
PY  - 2025
N1  - DKFZ-ZMBH Alliance
AB  - Conformational control of nascent chains is poorly understood. Chaperones are known to stabilize, unfold, and disaggregate polypeptides away from the ribosome. In comparison, much less is known about the elementary conformational control mechanisms at the ribosome. Yet, proteins encounter major folding and aggregation challenges during translation. Here, using selective ribosome profiling and optical tweezers with correlated single-molecule fluorescence, with dihydrofolate reductase (DHFR) as a model system, we show that the Escherichia coli chaperone trigger factor (TF) accelerates nascent chain folding. TF scans nascent chains by transient binding events, and then locks into a stable binding mode as the chain collapses and folds. This interplay is reciprocal: TF binding collapses nascent chains and stabilizes partial folds, while nascent chain compaction prolongs TF binding. Ongoing translation controls these cooperative effects, with TF-accelerated folding depending on the emergence of a peptide segment that is central to the core DHFR beta-sheet. The folding acceleration we report here impacts processes that depend on folding occurring cotranslationally, including cotranslational protein assembly, protein aggregation, and translational pausing, and may be relevant to other domains of life.
KW  - Protein Folding
KW  - Escherichia coli Proteins: metabolism
KW  - Escherichia coli Proteins: chemistry
KW  - Tetrahydrofolate Dehydrogenase: metabolism
KW  - Tetrahydrofolate Dehydrogenase: chemistry
KW  - Escherichia coli: metabolism
KW  - Ribosomes: metabolism
KW  - Peptidylprolyl Isomerase: metabolism
KW  - Protein Biosynthesis
KW  - Molecular Chaperones: metabolism
KW  - Protein Binding
KW  - chaperones (Other)
KW  - optical tweezers (Other)
KW  - protein folding (Other)
KW  - ribosomes (Other)
KW  - Escherichia coli Proteins (NLM Chemicals)
KW  - Tetrahydrofolate Dehydrogenase (NLM Chemicals)
KW  - trigger factor, E coli (NLM Chemicals)
KW  - Peptidylprolyl Isomerase (NLM Chemicals)
KW  - Molecular Chaperones (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40711920
DO  - DOI:10.1073/pnas.2422678122
UR  - https://inrepo02.dkfz.de/record/303193
ER  -