Molecular Chaperones HSP70 and HSP60 in Protein Folding and Membrane Translocation
Given the difficulties protein chemists may encounter when attempting to renature unfolded proteins in vitro,it is noteworthy that the acquisition of the correctly folded structure seems to be much less of a traumatic experience for a nascent polypeptide chain in vivo. Generally, unfolded polypeptides have the tendency to aggregate. The cellular environment with its extremely high concentration of total protein (~0.3 g/ml) and of newly-synthesized, folding chains (30–50 μM in Escherichia coli) may result in even further reduction of solubility and thus should strongly favor misfolding and aggregation of a folding protein (Zimmerman and Trach, 1991). Nevertheless, the yield of folded protein in vivo can reach almost 100% (Gething et al., 1986). It has become clear over recent years that the action of molecular chaperones, helper proteins which interact with folding intermediates and prevent unproductive off-pathway reactions (Ellis, 1987; Rothman, 1989; Gething and Sambrook, 1992), is essential in accomplishing this high efficiency of physiological protein folding.
KeywordsMolecular Chaperone Folding Protein Folding Pathway Folding Intermediate Chaperone DnaK
Unable to display preview. Download preview PDF.
- Chandrasekhar GN, Tilly K, Woolford C, Hendrix R, Georgopoulos C (1986) Purification and properties of the groES morphogenetic protein of Escherichia coli. J Biol Chem 21: 12414–12419Google Scholar
- Ellis RJ (1990) Molecular chaperones: the plant connection. Science 250:954–959 Flaherty KM, DeLuca-Flaherty, McKay DB (1990) Three-dimensional structure ofGoogle Scholar
- the ATPase fragment of a 70K heat-shock cognate protein. Nature 346:623–628Google Scholar
- Friedman, DE, Olson ER, Georgopoulos C, Tilly K, Herskowitz I, Banuett F (1984) Interactions of bacteriophage and host macromolecules in the growth of bacteriophage X.Microbiol Rev 48: 299–325Google Scholar
- Gething MJ, Sambrook J (1992) Protein folding in the cell. Nature 355:33–45 Hart! FU, Neupert W (1990) Protein sorting to mitochondria: evolutionary conservations of folding and assembly. Science 247: 930–938Google Scholar
- Langer T, Lu C, Echols H, Flanagan J, Hayer MK, Hartl FU (1992) Successive action of molecular chaperones DnaK, DnaJ and GroEL along the pathway of assisted protein folding. Nature 356: 683–689Google Scholar
- Liberek K, Marszalek J, Ang D, Georgopoulos C, Zylicz M (1991) Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proc Nati Acad Sci USA 88: 2874–2878Google Scholar
- Martin J, Langer T, Boteva R, Schramel A, Norwich AL, Hartl FU (1991 b) Chaperonin-mediated protein folding at the surface of groEL through a ‘molten globule’-like intermediate. Nature 352: 36–42Google Scholar
- Rassow J, Hartl FU, Guiard B, Pfanner N, Neupert W (1990) Polypeptides traverseGoogle Scholar
- the mitochondrial envelope in an extended state. FEBS Lett 275:190–194 Rothman JE (1989) Polypeptide chain binding proteins: catalysts of protein folding and related processes in cells. Cell 59: 591–601Google Scholar
- Wickner S, Hoskins J, McKenney K (1991 a) Function of DnaJ and DnaK as chaperones in origin-specific DNA binding by RepA. Nature 350: 165–167Google Scholar