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  • Cited by 8
  • Print publication year: 2005
  • Online publication date: August 2009

1 - Chaperone Function: The Orthodox View



The term molecular chaperone came into general use after the appearance of an article in Nature that suggested it was an appropriate phrase to describe a newly defined intracellular function – the ability of several unrelated protein families to assist the correct folding and assembly/disassembly of other proteins [1]. The identification of the chaperonin family of molecular chaperones in the following year [2] triggered a tidal wave of research in several laboratories aimed at unravelling how the GroEL/GroES chaperones, and later the DnaK/DnaJ chaperones, from Escherichia coli facilitate the folding of newly synthesised polypeptide chains and the refolding of denatured proteins. This wave continues to surge, with the result that much detailed information is available about the structure and function of those families of chaperone that assist protein folding [3].

It is now well established that a subset of proteins requires this chaperone function, not because chaperones provide steric information required for correct folding but because chaperones inhibit side reactions that would otherwise cause some of the chains to form non-functional aggregates. The number of different protein families described as chaperones is now more than 25 – some, but not all, of which are also stress proteins – and there is no slackening in the rate of discovery of new ones. The success of this wave of research has changed the paradigm of protein folding from the earlier view that it is a spontaneous self-assembly process to the current view that it is an assisted self-assembly process [4].

Ellis, R J. Proteins as molecular chaperones. Nature 1987, 328: 378–379
Hemmingsen, S M, Woolford, C, Vies, S M, Tilly, K, Dennis, D T, Georgopoulos, G C, Hendrix, R W and Ellis, R J. Homologous plant and bacterial proteins chaperone oligomeric protein assembly. Nature 1988, 333: 330–334
Hartl, F U and Hayer-Hartl, M. Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 2002, 295: 1852–1858
Ellis, R J and Hartl, F U. Protein folding and chaperones. Nature Encyclopedia of the Human Genome. Macmillan Publishers Ltd 2003, pp 806–810
Laskey, R A, Honda, B M and Finch, J T. Nucleosomes are assembled by an acidic protein that binds histones and transfers them to DNA. Nature 1978, 275: 416–420
Ellis R J. The general concept of molecular chaperones. In Ellis, R. J., Laskey, R. A. and Lorimer, G. H. (Eds.) Molecular Chaperones. Chapman and Hall for The Royal Society, London 1993, pp 1–5
Musgrove, J E and Ellis, R J. The rubisco large subunit binding protein. Phil Trans R Soc Lond B 1986, 313: 419–428
Ellis, R J and Hemmingsen, S M. Molecular chaperones: proteins essential for the biogenesis of some macromolecular structures. Trends Biochem Sci 1989, 14: 339–342
Puig, A and Gilbert, H F. Protein disulfide isomerase exhibits chaperone and antichaperone activity in the oxidative folding of lysozyme. J Biol Chem 1994, 269: 7764–7771
Ellis, R J. Steric chaperones. Trends Biochem Sci 1998, 23: 43–45
Finley, D, Bartel, B and Varshavsky, A. The tails of ubiquitin precursors are ribosomal proteins whose fusion to ubiquitin facilitates ribosome biogenesis. Nature 1989, 338: 394–401
Welch, W J. Role of quality control pathways in human diseases involving protein misfolding. Semin Cell Devel Biol 2004, 15: 31–38
Ellis, R J. Macromolecular crowding: obvious but underappreciated. Trends Biochem Sci 2001, 26: 597–603
Hartl, F U. Molecular chaperones in cellular protein folding. Nature 1996, 381: 571–579
Ellis, R J and Hartl, F U. Principles of protein folding in the cellular environment. Cur Opin Struct Biol 1999, 9: 102–110
Schlieker, C, Bukau, B and Mogk, A. Prevention and reversion of protein aggregation by molecular chaperones in the E. coli cytosol; implications for their applicability in biotechnology. J Biotech 2002, 96: 13–21
Beatrix, B, Sakai, H and Wiedmann, M. The α and β subunits of the nascent polypeptide complex have distinct functions. J Biol Chem 2000, 275: 37838–37845
Deuerling, E, Schulze-Specking, A, Tomoyasu, A, Mogk, A and Bukau, B. Trigger factor and DnaK cooperate in folding of newly synthesized proteins. Nature 1999, 400: 693–696
Teter, S A, Houry, W A, Ang, D A, Tradler, T, Rockabrand, D, Fischer, G, Blum, P, Georgopoulos, C and Hartl, F U. Polypeptide flux through bacterial hsp70: DnaK cooperates with trigger factor in chaperoning nascent chains. Cell 1999, 97: 755–765
Bukau, B and Horwich, A L. The Hsp70 and Hsp60 chaperone machines. Cell 1998, 92: 351–366
Sondermann, H, Scheufler, C, Schneider, C, Hohfeld, J, Hartl, F U and Moarefi, I. Structure of a Bag/hsc70 complex: convergent functional evolution of hsp70 nucleotide exchange factors. Science 2001, 291: 1553–1557
Xu, Z, Horwich, A L and Sigler, P B. The crystal structure of the asymmetric GroEL-GroES- (ADP)7 chaperonin complex. Nature 1997, 388: 741–750
Ellis, R J. Protein folding: importance of the Anfinsen cage. Cur Biol 2003, 13: R881–R883
Martin, J and Hartl, F U. The effect of macromolecular crowding on chaperonin-mediated protein folding. Proc Natl Acad Sci USA 1997, 94: 1107–1112
Farr, G W, Fenton, W A, Rospert, S and Horwich, A L. Folding with and without encapsulation by cis and trans-only GroEL-GroES complexes. EMBO J 2001, 22: 3220–3230
Brinker, A, Pfeifer, G, Kerner, M J, Naylor, D J, Hartl, F U and Hayer-Hartl, M. Dual function of protein confinement in chaperonin-assisted protein folding. Cell 2001, 107: 223–233
Takagi, F, Koga, N and Takada, S. How protein thermodynamics and folding are altered by the chaperonin cage: molecular simulations. Proc Natl Acad Sci USA 2003, 100: 11367–11372
Thirumalai, D and Lorimer, G H. Chaperonin-mediated protein folding. Ann Rev Biophys Biomol Struct 2001, 30: 245–269
Young, J C, Moarefi, I and Hartl, F U. Hsp90: a specialized but essential protein-folding tool. J Cell Biol 2001, 154: 267–273
Smith, D F. Chaperones in progesterone receptor complexes. Semin Cell Devel Biol 2000, 11: 45–52
Csermley, P. Chaperone overload is a possible contributor to ‘civilization diseases’. Trends Genetics 2001, 17: 701–704
Soti, C and Csermley, P. Molecular chaperones and the aging process. Biogerontology 2000, 1: 225–233
Glover, J R and Tkach, J M. Crowbars and rachets: hsp100 chaperones as tools in reversing aggregation. Biochem Cell Biol 2001, 79: 557–568
Parsell, D A, Kowal, A S, Singer, M A and Lindquist, S. Protein disaggregation by heat shock protein hsp104. Nature 1994, 372: 475–477
Yoshida, N, Oeda, K, Watanabe, E, Mikami, T, Fukita, Y, Nishimura, K, Komai, K and Matsuda, K. Protein function. Chaperonin turned insect toxin. Nature 2001, 411: 44