Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein

@article{Hartl2002MolecularCI,
  title={Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein},
  author={F. Ulrich Hartl and Manajit Hayer‐Hartl},
  journal={Science},
  year={2002},
  volume={295},
  pages={1852 - 1858}
}
Efficient folding of many newly synthesized proteins depends on assistance from molecular chaperones, which serve to prevent protein misfolding and aggregation in the crowded environment of the cell. Nascent chain–binding chaperones, including trigger factor, Hsp70, and prefoldin, stabilize elongating chains on ribosomes in a nonaggregated state. Folding in the cytosol is achieved either on controlled chain release from these factors or after transfer of newly synthesized proteins to downstream… 

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References

SHOWING 1-10 OF 78 REFERENCES

Folding of newly translated proteins in vivo: the role of molecular chaperones.

  • J. Frydman
  • Biology
    Annual review of biochemistry
  • 2001
Genetic and biochemical analysis shows that several distinct chaperone systems, including Hsp70 and the cylindrical chaperonins, assist the folding of proteins upon translation in the cytosol of both prokaryotic and eukaryotic cells.

Molecular chaperones in cellular protein folding

Significant progress has been made in the understanding of the ATP-dependent mechanisms used by the Hsp70 and chaperonin families of molecular chaperones, which can cooperate to assist in folding new polypeptide chains.

In vivo newly translated polypeptides are sequestered in a protected folding environment

It is concluded that de novo protein folding occurs in a protected environment created by a highly processive chaperone machinery and is directly coupled to translation.

Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones

The folding of polypeptides emerging from ribosomes was analysed in a mammalian translation system using firefly luciferase as a model protein and found that the ordered assembly of these components on the nascent chain forms a high molecular mass complex.

Prefoldin–Nascent Chain Complexes in the Folding of Cytoskeletal Proteins

It is concluded that PFD functions by selectively targeting nascent actin and tubulin chains pending their transfer to CCT for final folding and/or assembly.

Hsp90 & Co. - a holding for folding.

  • J. Buchner
  • Biology
    Trends in biochemical sciences
  • 1999

Review: mechanisms of disaggregation and refolding of stable protein aggregates by molecular chaperones.

Active disaggregation by the chaperone network can serve as a central cellular tool for the recovery of native proteins from stress-induced aggregates and actively remove disease-causing toxic aggregates, such as polyglutamine-rich proteins, amyloid plaques, and prions.
...