Trigger factor accelerates nascent chain compaction and folding
Katharina Till (AMOLF Institute for Atomic and Molecular Physics)
Anne Bart Seinen (AMOLF Institute for Atomic and Molecular Physics)
Florian Wruck (AMOLF Institute for Atomic and Molecular Physics, TU Delft - BN/Sander Tans Lab)
Vanda Sunderlikova (AMOLF Institute for Atomic and Molecular Physics)
Carla V. Galmozzi (University of Seville, University of Heidelberg)
Alexandros Katranidis (Forschungszentrum Jülich)
Bernd Bukau (University of Heidelberg)
Günter Kramer (University of Heidelberg)
Sander J. Tans (Kavli institute of nanoscience Delft, AMOLF Institute for Atomic and Molecular Physics, TU Delft - BN/Sander Tans Lab)
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Abstract
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.
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