Trigger factor accelerates nascent chain compaction and folding

• 成果类型: Article
• 署名作者: Till, Katharina; Seinen, Anne-Bart; Wruck, Florian; Sunderlikova, Vanda; Galmozzi, Carla V.; Katranidis, Alexandros; Bukau, Bernd; Kramer, Guenter; Tans, Sander J.
• 署名单位: AMOLF; Helmholtz Association; German Cancer Research Center (DKFZ); Consejo Superior de Investigaciones Cientificas (CSIC); University of Sevilla; CSIC-JA-USE - Instituto de Biomedicina de Sevilla (IBIS); Delft University of Technology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13324
• DOI: 10.1073/pnas.2422678122
• 发表日期: 2025-07-29
• 关键词: escherichia-coli; molecular chaperones; protein; ribosome; groel; intermediate; mechanism; reveals; cavity; hsp70

摘要

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 comwith TF- accelerated folding depending on the emergence of a peptide segment that is 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.