Bacterial RF3 senses chaperone function in co-translational folding.
Liang Zhao1, Marie-Pierre Castanié-Cornet2, Sneha Kumar1
1Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Molecular Cell
|June 9, 2021
Summary
The ribosome can detect misfolding nascent polypeptides (NCs) and trigger translation termination. This process involves the release factor RF3, preventing misfolded protein buildup and maintaining cell proteostasis.
Area of Science:
- Molecular biology
- Cellular biology
- Protein biochemistry
Background:
- Molecular chaperones are essential for correct protein folding during translation.
- The ribosome's ability to sense and respond to chaperone defects and misfolding nascent chains (NCs) remains largely unexplored.
Purpose of the Study:
- To investigate the ribosome-associated chaperone network in E. coli.
- To understand the consequences of chaperone dysfunction on translation and proteostasis.
Main Methods:
- Quantitative proteomics was employed to analyze the ribosome-associated chaperone network.
- The study examined the impact of co-translational chaperone defects and amino acid analog incorporation on nascent chain processing.
Main Results:
- Trigger factor and the DnaK (Hsp70) system are primary NC-binding chaperones.
- HtpG (Hsp90), GroEL, and ClpB become important when DnaK is deficient.
- Misfolding triggers recruitment of the non-canonical release factor RF3, which cooperates with RF2 for chain termination.
Conclusions:
- RF3 recognizes aberrant NCs and mediates termination, preventing misfolded protein accumulation.
- This RF3-mediated termination is critical for maintaining proteostasis and cell survival under chaperone-limited conditions.
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