Chaperones, molecular

Molecular chaperones are able to temporarily stabihze unfolded or partially folded proteins and prevent inappropriate inter- and intramolecular interactions. They reduce the free concentration of aggregation-sensitive folding in- 

Another important protein of the Clp family is ClpB which possesses ATPase activity. In a clpB mutation, 45% of the denatured and aggregated protein arising transiently after the transfer of an E. coli culture from 30 to 45 °C is stabilized [14]. ClpB seems to play an important role in the renaturation or proteolysis of the aggregated proteins, but the mechanism of action of ClpB is not yet known. One can suppose that it might participate in the resolubilization of aggregated proteins. 

It is generally believed that energy-independent chaperones are unable to allow refolding of non-native proteins. They bind to hydrophobic surfaces of denatured proteins to prevent aggregation and pass them to energy-dependent chaperones such as the DnaK or the GroE chaperone machines. 

6 Proteins Involved in Subunit Assembly in vivo 3.6.1 Molecular Chaperones 

One of the greatest mysteries concerning the quaternary structure of oligomeric proteins has been the method by which these proteins fold to assume their active conformation in the 

Protein family PDI Cyclophilin PPIase FKBP PPIase Hsp60 Hsp70 Hsp90 

Cytosol Thioredoxin PPIase b GroEL DnaK HtpG (C62.5) 

Cytosol Cphlp (Cprlp) Fkblp (Fkrlp) Ssal-4p Hsp83 

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Hartl, F.U. Molecular chaperones in cellular protein folding. Nature 381 571-580, 1996. 

Zhu, X., et al. Structural analysis of substrate binding by the molecular chaperone DnaK. Science 272 1606-1614, 1996. 

Molecular Chaperones Proteins That Help Fold Glohular Proteins... 

The way in which molecular chaperones interact with polypeptides during the folding process is not completely understood. What is clear is that chaperones bind effectively to the exposed hydrophobic regions of partially folded structures. These folding intermediates are less compact than the native folded proteins. They contain large amounts of secondary and even some tertiary... 

Flynn, G. C., Beckers, C. J. M., Baase, W. A., and Dahlquist, F. W. (1993). Individual subunits of bacterial luciferase are molten globules and interact with molecular chaperones. Proc. Natl. Acad. Sci. USA 90 10826-10830. 

Molecular chaperone (relative molecular mass 78 K) found in the lumen of the ER. BiP is related to the Hsp70 family of heat-shock proteins and was originally described as immunoglobulin heavy chain binding protein. 

Molecular chaperones, stress proteins (note not all stress proteins are molecular chaperones and not all molecular chaperones are stress proteins) Heat shock proteins (Hsp) Polypeptide chain binding proteins... 

The term molecular chaperone was coined by Ron A. Laskey and coworkers in 1978 to describe the... 

Today, molecular chaperones are divided into three principle classes, according to their mode of action (Table 1). The one class comprises the chaperonins or HsplOO protein family members. Chaperonins are oligomeric proteins, composed of two rings placed... 

Chaperones. Table 1 Molecular Chaperones in Humans (note this list is not meant to be exhaustive). Synonyms are given in parentheses... 

Brodsky JL, Chiosis G (2006) Hsp70 molecular chaperones emerging roles in human disease and identification of small molecule modulators. Curr Top Med Chem 6 1215-1225... 

A small compound that mimicks a molecular chaperone in activity. 

A nonsubstrate protein that interacts specifically with a molecular chaperone, and is important for efficient chaperone function. 

Hsp70 is a molecular chaperone (relative molecular mass 70 kD) found in different compartments of eucaryotic cells. Hsp70 was originally described as heat shock protein 70. 

Hsp90 is a molecular chaperon required for the refolding of proteins in cells exposed to environmental stress. It contains an ATP-binding pocket in its amino terminus. Several natural products, for example radicicol (230) (Scheme 48), bind to this pocket and inhibit its chaperon function, which is mirrored in enhanced proteosomal degradation of Hsp90 client proteins, so that compounds like 230 are of interest as novel anticancer agents. 

The efficient uptake of precursor proteins depends on their presentation in a translocation competent state. This is maintained in vivo by the specific interaction with a highly conserved group of proteins, the heat-shock or stress related proteins (hps70s). These act as molecular chaperones and interact with the proteins to maintain them in a correctly folded state, a process which is ATP dependent. 

Welch, W.J. (1991). The role of heat shock proteins as molecular chaperones Curr. Opin. Cell Biol. 3, 1033-1038. 

Both the heat and cold shock response are universal and have been studied extensively. The major heat shock proteins (HSPs) are highly conserved. They are involved in the homeostatic adaptation of cells to harsh environmental conditions. Some act as molecular chaperones for protein folding, while others are involved in the processing of denatured polypeptides whose accumulation would be deleterious. The cold shock results in the transient induction of cold shock proteins (CSPs), which include a family of small acidic proteins carrying the cold shock domain. The CSPs appear to be involved in various cellular functions such as transcription, translation and DNA recombination. 

Frydman J Folding of newly translated proteins in vivo The role of molecular chaperones. Annu Rev Biochem 2001 70 603. Radord S Protein folding Progress made and promises ahead. 

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