Real-time observation of trigger factor function on translating ribosomes

Christian M. Kaiser, Hung Chun Chang, Vishwas R. Agashe, Sathish K. Lakshmipathy, Stephanie A. Etchells, Manajit Hayer-Hartl, F. Ulrich Hartl, José M. Barral

    Research output: Contribution to journalArticle

    157 Citations (Scopus)

    Abstract

    The contribution of co-translational chaperone functions to protein folding is poorly understood. Ribosome-associated trigger factor (TF) is the first molecular chaperone encountered by nascent polypeptides in bacteria. Here we show, using fluorescence spectroscopy to monitor TF function and structural rearrangements in real time, that TF interacts with ribosomes and translating polypeptides in a dynamic reaction cycle. Ribosome binding stabilizes TF in an open, activated conformation. Activated TF departs from the ribosome after a mean residence time of ∼10 s, but may remain associated with the elongating nascent chain for up to 35 s, allowing entry of a new TF molecule at the ribosome docking site. The duration of nascent-chain interaction correlates with the occurrence of hydrophobic motifs in translating polypeptides, reflecting a high aggregation propensity. These findings can explain how TF prevents misfolding events during translation and may provide a paradigm for the regulation of nucleotide-independent chaperones.

    Original languageEnglish (US)
    Pages (from-to)455-460
    Number of pages6
    JournalNature
    Volume444
    Issue number7118
    DOIs
    StatePublished - Nov 23 2006

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    Ribosomes
    Observation
    Peptides
    Molecular Chaperones
    Fluorescence Spectrometry
    Protein Folding
    Nucleotides
    Bacteria

    ASJC Scopus subject areas

    • General

    Cite this

    Kaiser, C. M., Chang, H. C., Agashe, V. R., Lakshmipathy, S. K., Etchells, S. A., Hayer-Hartl, M., ... Barral, J. M. (2006). Real-time observation of trigger factor function on translating ribosomes. Nature, 444(7118), 455-460. https://doi.org/10.1038/nature05225

    Real-time observation of trigger factor function on translating ribosomes. / Kaiser, Christian M.; Chang, Hung Chun; Agashe, Vishwas R.; Lakshmipathy, Sathish K.; Etchells, Stephanie A.; Hayer-Hartl, Manajit; Hartl, F. Ulrich; Barral, José M.

    In: Nature, Vol. 444, No. 7118, 23.11.2006, p. 455-460.

    Research output: Contribution to journalArticle

    Kaiser, CM, Chang, HC, Agashe, VR, Lakshmipathy, SK, Etchells, SA, Hayer-Hartl, M, Hartl, FU & Barral, JM 2006, 'Real-time observation of trigger factor function on translating ribosomes', Nature, vol. 444, no. 7118, pp. 455-460. https://doi.org/10.1038/nature05225
    Kaiser CM, Chang HC, Agashe VR, Lakshmipathy SK, Etchells SA, Hayer-Hartl M et al. Real-time observation of trigger factor function on translating ribosomes. Nature. 2006 Nov 23;444(7118):455-460. https://doi.org/10.1038/nature05225
    Kaiser, Christian M. ; Chang, Hung Chun ; Agashe, Vishwas R. ; Lakshmipathy, Sathish K. ; Etchells, Stephanie A. ; Hayer-Hartl, Manajit ; Hartl, F. Ulrich ; Barral, José M. / Real-time observation of trigger factor function on translating ribosomes. In: Nature. 2006 ; Vol. 444, No. 7118. pp. 455-460.
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