Function of trigger factor and DnaK in multidomain protein folding: Increase in yield at the expense of folding speed

Vishwas R. Agashe, Suranjana Guha, Hung Chun Chang, Pierre Genevaux, Manajit Hayer-Hartl, Markus Stemp, Costa Georgopoulos, F. Ulrich Hartl, José M. Barral

    Research output: Contribution to journalArticlepeer-review

    156 Scopus citations

    Abstract

    Trigger factor and DnaK protect nascent protein chains from misfolding and aggregation in the E. coli cytosol, but how these chaperones affect the mechanism of de novo protein folding is not yet understood. Upon expression under chaperone-depleted conditions, multidomain proteins such as bacterial β-galactosidase (β-gal) and eukaryotic luciferase fold by a rapid but inefficient default pathway, tightly coupled to translation. Trigger factor and DnaK improve the folding yield of these proteins but markedly delay the folding process both in vivo and in vitro. This effect requires the dynamic recruitment of additional trigger factor molecules to translating ribosomes. While β-galactosidase uses this chaperone mechanism effectively, luciferase folding in E. coli remains inefficient. The efficient cotranslational domain folding of luciferase observed in the eukaryotic system is not compatible with the bacterial chaperone system. These findings suggest important differences in the coupling of translation and folding between bacterial and eukaryotic cells.

    Original languageEnglish (US)
    Pages (from-to)199-209
    Number of pages11
    JournalCell
    Volume117
    Issue number2
    DOIs
    StatePublished - Apr 16 2004

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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