Concerted action of the ribosome and the associated chaperone Trigger Factor confines nascent polypeptide folding

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2012
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Hoffmann, Anja
Becker, Annemarie H.
Zachmann-Brand, Beate
Bukau, Bernd
Kramer, Günter
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Molecular Cell. 2012, 48(1), pp. 63-74. ISSN 1097-2765. eISSN 1097-4164. Available under: doi: 10.1016/j.molcel.2012.07.018
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How nascent polypeptides emerging from ribosomes fold into functional structures is poorly understood. Here, we monitor disulfide bond formation, protease resistance, and enzymatic activity in nascent polypeptides to show that in close proximity to the ribosome, conformational space and kinetics of folding are restricted. Folding constraints decrease incrementally with distance from the ribosome surface. Upon ribosome binding, the chaperone Trigger Factor counters folding also of longer nascent chains, to extents varying between different chain segments. Trigger Factor even binds and unfolds pre-existing folded structures, the unfolding activity being limited by the thermodynamic stability of nascent chains. Folding retardation and unfolding activities are not shared by the DnaK chaperone assisting later folding steps. These ribosome- and Trigger Factor-specific activities together constitute an efficient mechanism to prevent or even revert premature folding, effectively limiting misfolded intermediates during protein synthesis.

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ISO 690HOFFMANN, Anja, Annemarie H. BECKER, Beate ZACHMANN-BRAND, Elke DEUERLING, Bernd BUKAU, Günter KRAMER, 2012. Concerted action of the ribosome and the associated chaperone Trigger Factor confines nascent polypeptide folding. In: Molecular Cell. 2012, 48(1), pp. 63-74. ISSN 1097-2765. eISSN 1097-4164. Available under: doi: 10.1016/j.molcel.2012.07.018
BibTex
@article{Hoffmann2012-10-12Conce-21403,
  year={2012},
  doi={10.1016/j.molcel.2012.07.018},
  title={Concerted action of the ribosome and the associated chaperone Trigger Factor confines nascent polypeptide folding},
  number={1},
  volume={48},
  issn={1097-2765},
  journal={Molecular Cell},
  pages={63--74},
  author={Hoffmann, Anja and Becker, Annemarie H. and Zachmann-Brand, Beate and Deuerling, Elke and Bukau, Bernd and Kramer, Günter}
}
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