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 journalArticle

147 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Protein folding
Protein Folding
Luciferases
Galactosidases
Escherichia coli
Proteins
Eukaryotic Cells
Ribosomes
Cytosol
Agglomeration
Molecules

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Agashe, V. R., Guha, S., Chang, H. C., Genevaux, P., Hayer-Hartl, M., Stemp, M., ... Barral, J. M. (2004). Function of trigger factor and DnaK in multidomain protein folding: Increase in yield at the expense of folding speed. Cell, 117(2), 199-209. https://doi.org/10.1016/S0092-8674(04)00299-5

Function of trigger factor and DnaK in multidomain protein folding : Increase in yield at the expense of folding speed. / Agashe, Vishwas R.; Guha, Suranjana; Chang, Hung Chun; Genevaux, Pierre; Hayer-Hartl, Manajit; Stemp, Markus; Georgopoulos, Costa; Hartl, F. Ulrich; Barral, José M.

In: Cell, Vol. 117, No. 2, 16.04.2004, p. 199-209.

Research output: Contribution to journalArticle

Agashe, VR, Guha, S, Chang, HC, Genevaux, P, Hayer-Hartl, M, Stemp, M, Georgopoulos, C, Hartl, FU & Barral, JM 2004, 'Function of trigger factor and DnaK in multidomain protein folding: Increase in yield at the expense of folding speed', Cell, vol. 117, no. 2, pp. 199-209. https://doi.org/10.1016/S0092-8674(04)00299-5
Agashe, Vishwas R. ; Guha, Suranjana ; Chang, Hung Chun ; Genevaux, Pierre ; Hayer-Hartl, Manajit ; Stemp, Markus ; Georgopoulos, Costa ; Hartl, F. Ulrich ; Barral, José M. / Function of trigger factor and DnaK in multidomain protein folding : Increase in yield at the expense of folding speed. In: Cell. 2004 ; Vol. 117, No. 2. pp. 199-209.
@article{3f0f57d3299745c4b3d0350c1d6f6086,
title = "Function of trigger factor and DnaK in multidomain protein folding: Increase in yield at the expense of folding speed",
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.",
author = "Agashe, {Vishwas R.} and Suranjana Guha and Chang, {Hung Chun} and Pierre Genevaux and Manajit Hayer-Hartl and Markus Stemp and Costa Georgopoulos and Hartl, {F. Ulrich} and Barral, {Jos{\'e} M.}",
year = "2004",
month = "4",
day = "16",
doi = "10.1016/S0092-8674(04)00299-5",
language = "English (US)",
volume = "117",
pages = "199--209",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Function of trigger factor and DnaK in multidomain protein folding

T2 - Increase in yield at the expense of folding speed

AU - Agashe, Vishwas R.

AU - Guha, Suranjana

AU - Chang, Hung Chun

AU - Genevaux, Pierre

AU - Hayer-Hartl, Manajit

AU - Stemp, Markus

AU - Georgopoulos, Costa

AU - Hartl, F. Ulrich

AU - Barral, José M.

PY - 2004/4/16

Y1 - 2004/4/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=1942421714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1942421714&partnerID=8YFLogxK

U2 - 10.1016/S0092-8674(04)00299-5

DO - 10.1016/S0092-8674(04)00299-5

M3 - Article

C2 - 15084258

AN - SCOPUS:1942421714

VL - 117

SP - 199

EP - 209

JO - Cell

JF - Cell

SN - 0092-8674

IS - 2

ER -