The basic protein folding problem required reevaluation when molecular chaperones and folding ligands were discovered to play an important role in folding in vivo in cells (Ellis and Van der Vies, 1991; Zeilstra-Ryalls et al.,1991; Nisslon and Anderson, 1991; Gething and Sambrook, 1992; Hartle and Martin, 1992; Jaenicke, 1993). Many chaperones were originally discovered as heat-shock proteins. Of the chaperones, the chaperonin family has the most distinctive structure: they contain large multisubunit assemblies essential in mediation of ATP-dependent polypeptide chain folding in a variety of cellular compartments. Two families of chaperones have been identified: the Hsp60 class, with membranes in the bacterial cytoplasm (GroEL) and in the endosymbiotically derived mitochondria (Hsp60, cph60) and chloroplasts (Rubisco binding protein), TF55/TCPI family in thermophilic archaeans and the evolutionarily connected eukaryotic cytosol. Members of both families consist of two stacked rings (Hendrix, 1979; McMullen and Hallberg, 1987; Pushkin et al., 1982; Trent et al., 1991; Goo et al., 1992), each ring containing radially arranged subunits of relative molecular weight ~60,000 (M r~60k), with seven identical subunits per ring in the GroEL/Hsp60 family (Hendrix, 1979; McMullen and Hallberg, 1987; Pushkin, et al., 1982). Functioning like other molecular chaperones, they appear to act by inhibiting incorrect folding pathways, and are known to bind to a wide variety of nonnative proteins (Saibil and Wood, 1993a,b). In vitro studies with polypeptides diluted from denaturant show that nonnative folding intermediates bind to GroEL with a stoichiometry of one or two polypeptides per GroEL 14-mer (Gouloubinoff et al., 1989a,ó; Martin et al., 1991; Mendoza et al., 1991; Bochkareva et al., 1992).
KeywordsCircular Dichroism Molecular Chaperone Molten Globule Circular Dichroism Analysis Nonnative Protein
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- Bolotina, I. A., Tchekhov, V. O., Lugauskas, V. J., and Ptitsyn, O. B., 1980, Determination of the secondary structure of proteins from circular dichroism spectra III. Protein derived spectra for antiparallel and parallel r3-structures, Mol. Biol. (Moscow) 14: 902–909.Google Scholar
- Horowich, A. L., Caplan, S., Wall, J. S., and Hartl, F.-U., 1992, Chaperonin mediated protein folding, in: Membrane Biogenesis and Protein Targeting (Neupert, W., and Lill, R., eds.), Elsevier, Amsterdam. Ishi, N., Taguchi, H., Sasabe, H., and Yoshida, M., 1994, Folding intermediate binds to the bottom of bullet-shaped holo-chaperonin and is readily accessible to antibody, J. Mol. Biol. 236: 691–696.Google Scholar
- Kumamoto, C. A., and Francetic, 0., 1993, Highly selective binding of nascent polypeptides by an Escherichia coli chaperone protein in vivo, J. Bacteriol. 175: 2184–2188.Google Scholar
- Lissen, N. M., Venyaminov, S. Y., and Girshovich, A. S., 1990, (Mg-ATP)-dependent self-assembly of molecular chaperone GroEL, Nature 348: 339–342.Google Scholar
- McMullen, T. W., and Hallberg, L., 1987, A normal mitochondrial protein is selectively synthesized and accumulated during heat shock in Tetrahymena thermophila, Mol. Cell Biol. 7: 4414–4423.Google Scholar
- Park, K., Flynn, G. C., Rothman, J. E., and Fasman, G. D., 1993, Conformational change of chaperone Hsc70 upon binding to a decapeptide: A circular dichroism study, Protein Sci. 2:325–330. Perczel, A., Hollosi, M., Tusnady, G., and Fasman, G. D., 1989, Convex constraints decomposition of circular dichroism curves of proteins, Croat. Chim. Acta 62: 189–200.Google Scholar
- Zahn, R., Harris, J. R., Pfeifer, G., Plucktun, A., and Baumeister, W., 1993, 2-Dimensional crystals of the molecular chaperone GroEL reveal structural plasticity, J. Mol. Biol. 229: 579–584.Google Scholar
- Zardemta, G., and Horowitz, P. M., 1992, Micelle-assisted folding, J. Biol. Chem. 219: 11–23.Google Scholar