Protein folding chaperons

Nonetheless, this cell-free assay conversion of recombinant protein provides strong evidence for the protein-only hypothesis, but demonstration of true infectivity of the converted material is still necessary. Furthermore, DebBurman et al (1997) have shown that GroEL, a known protein-folding chaperone, increases the efficiency of conversion in the cell-free assay but only in the presence of PrP . ... 

Little was known about protein folding. Chaperone proteins are often necessary for correct folding of proteins and subunit assembly. In bacteria, there is low... 

Most reactions in cells are carried out by enzymes [1], In many instances the rates of enzyme-catalysed reactions are enhanced by a factor of a million. A significantly large fraction of all known enzymes are proteins which are made from twenty naturally occurring amino acids. The amino acids are linked by peptide bonds to fonn polypeptide chains. The primary sequence of a protein specifies the linear order in which the amino acids are linked. To carry out the catalytic activity the linear sequence has to fold to a well defined tliree-dimensional (3D) stmcture. In cells only a relatively small fraction of proteins require assistance from chaperones (helper proteins) [2]. Even in the complicated cellular environment most proteins fold spontaneously upon synthesis. The detennination of the 3D folded stmcture from the one-dimensional primary sequence is the most popular protein folding problem. 

How does the GroEL-GroES complex function as a chaperone to assist protein folding Although several aspects of the mechanism are not clear, the main features of the functional cycle are known. The first step is the... 

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

A number of different low molecular weight compounds are known to stablize proteins in their native conformation and, therefore, may be effective in correcting of protein folding abnormalities in vivo. Relevant compounds are iV-acetyl-L-lysine, L-camitine, taurine, betaine, ectoine, and hydroxy-ectoine [4]. Some of these chemical chaperones and pharmacological chaperones are already used in clinical trials to combat protein folding diseases, such as cystic fibrosis. 

Welch W, Brown CR (1996) Influence of molecular and chemical chaperones on protein folding. Cell Stress Chaperones 1 109-115... 

Craig, E.A. (1993).Chaperones—helpers along the pathways to protein folding. Science 260, 1902-1903. 

Langer, T., Lu., C, Echols, H., Flanagan, J, Hayer, M.K., Hartl, F.-U. (1992). Successive action of Dnak, DnaJ, GroEL along the pathway of chaperone mediated protein folding. Nature 356, 683-689. 

Wiech, H., Buchner, J., Zimmermann, R., Jakob, U. (1992). Hsp90 chaperones protein folding in vitro. Nature 358,169-170. 

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. 

Folding chaperons Prefolding as in eukaryotes Different heat shock proteins (chaperones)... 

Proteins translated on the RER generally fold and assemble into subimits in the ER before being transferred to the Golgi apparatus. Other proteins fold in the cytoplasm. Molecular chaperones (proteins such as calnexin and BiP) assist in this process of protein folding. Proteins that are misfolded are targeted for destruction by ubiquitin and digested in cytoplasmic protein-digesting complexes called proteasomes. 

A new insight into the problem of insolnbUity of heterologous proteins has evolved from further information regarding the in vivo function of molecnlar chaperones in protein folding. As reviewed by Baneyx, co-expression of chaperones in the bacterial system can improve the folding and hence the yield of heterologous proteins [96]. 

To prevent incorrect folding of the growing protein during protein biosynthesis, chaperones (see B) in the lumen of the rER bind to the peptide chain and stabilize it until translation has been completed. Binding protein (BiP) is an important chaperone in the ER. 

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