Molecular chaperones in cellular protein folding

  title={Molecular chaperones in cellular protein folding},
  author={F. Ulrich Hartl},
  • F. Hartl
  • Published 13 June 1996
  • Biology, Chemistry
  • Nature
The folding of many newly synthesized proteins in the cell depends on a set of conserved proteins known as molecular chaperones. These prevent the formation of misfolded protein structures, both under normal conditions and when cells are exposed to stresses such as high temperature. 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… 

Protein folding in vivo: the importance of molecular chaperones.

Chaperone-assisted protein folding.

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

Understanding how the thousands of different proteins synthesized in a cell use this chaperone machinery has profound implications for biotechnology and medicine.

Protein Folding and Chaperones

The specific conformation characteristic of each protein is determined by the amino acid sequence of that protein by the process of protein folding. Molecular chaperones use two distinct mechanisms

From the cradle to the grave: molecular chaperones that may choose between folding and degradation

A novel concept for the regulation of the eukaryotic Hsp70 and Hsp90 chaperone systems during protein folding and protein degradation is presented.

Chaperones, Chaperonin and Heat‐Shock Proteins

The protein folding of a nascent polypeptide is the decoding of the linear information contained in the primary sequence into the native three-dimensional conformation. Chaperone proteins and folding

Protein folding in the cytoplasm and the heat shock response.

The mechanisms that ensure the maintenance of a functional proteome under normal and stress conditions are also of great medical relevance, as the aggregation of proteins that escape the cellular quality control underlies a range of debilitating diseases, including many age-of-onset neurodegenerative disorders.

Protein folding: Who chaperones nascent chains in bacteria?

Structures and Functions of Chaperones and Chaperonins (Review)

Molecular chaperones are a group of relatively recently discovered proteins that control the assembling of native structures and remodel protein molecules that have wrong conformations.



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.

Protein folding in the cell

Folding and assembly of polypeptides in vivo involves other proteins, many of which belong to families that have been highly conserved during evolution.

Proper and improper folding of proteins in the cellular environment.

Protein folding in the cellular environment involves an interplay between the intrinsic biophysical properties of a protein, in both its folded and unfolded states, and various accessory proteins

Peptide-binding specificity of the molecular chaperone BiP

The specificity for peptide ligands is investigated using a set of peptides of random sequence but defined chain length and selects for aliphatic residues and accommodates them in an environment energetically equivalent to the interior of a folded protein.

Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding

The main stress proteins of Escherichia coli function in an ordered protein-folding reaction and this sequential mechanism of chaperone action may represent an important pathway for the folding of newly synthesized polypeptides.

Protein folding in mitochondria requires complex formation with hsp60 and ATP hydrolysis

It is proposed that mitochondrial heat-shock protein hsp60 catalyses protein folding in an ATP-mediated reaction, followed by release of the bound polypeptides.

Control of folding and membrane translocation by binding of the chaperone DnaJ to nascent polypeptides.

It is shown by crosslinking that the chaperone DnaJ binds nascent ribosome-bound polypeptide chains as short as 55 residues, which helps clarify the stage in its biogenesis at which the folding protein makes first contact with these components.

Roles of molecular chaperones in protein degradation

It now appears that molecular chaperones facilitate protein degradation in many different ways, and examples where molecular chapers increase the susceptibility of certain substrate proteins to proteolytic attack are cited.