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

  title={Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein},
  author={F. Ulrich Hartl and Manajit Hayer‐Hartl},
  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… 

Chaperone-Assisted Folding of Newly Synthesized Proteins in the Cytosol

Recent advances have determined the atomic structure of the Trigger Factor, providing new, exciting insights into the role of ribosome-associated chaperones in co-translational protein folding.

Molecular chaperone functions in protein folding and proteostasis.

This review focuses on recent advances in understanding the mechanisms of chaperone action in promoting and regulating protein folding and on the pathological consequences of protein misfolding and aggregation.

Functions of Ribosome-Associated Chaperones and their Interaction Network

While the bacteria-specific chaperone trigger factor binds to almost every nascent polypeptide made by ribosomes except for membrane proteins, the substrate pool of the two eukaryotic ribosome-associated chaperones systems, nascent polyPEptide-associated complex (NAC) and ribosom-associatedcomplex (RAC), is more distinct.

Protein Folding In Vivo

Molecular chaperones prevent the potentially toxic aggregation of newly synthesised polypeptides during translation and when mature proteins unfold during stress conditions or ageing.

Chaperones in control of protein disaggregation

This work focuses on the molecular mechanisms by which heat‐shock protein 70 (Hsp70), Hsp100 and small Hsp chaperones liberate and refold polypeptides trapped in protein aggregates.

Molecular guardians for newborn proteins: ribosome-associated chaperones and their role in protein folding

Structural insights into Trigger Factor reveal an intricate cradle-like structure that, together with the exit site of the ribosome, forms a protected environment for the folding of newly synthesized proteins.

A cradle for new proteins: trigger factor at the ribosome.

Cofactors and co-chaperones of the chaperonin CCT: mechanistic insights and in vivo relevance

The role of C'C'T co-chaperones (PFD) and cofactors (PhLP) in modulating the chaperonin's function is illuminated and new research prospects are opened up by identifying novel genetic interactors of CCT.



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  • J. Frydman
  • Biology
    Annual review of biochemistry
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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.

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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.

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  • Biology
    Trends in biochemical sciences
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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.