Biopolym. Cell. 2001; 17(5):356-362.
1Erko V. N.
  1. Institute of Plant Physiology and Genetics, NAS of Ukraine
    31/17, Vasylkivska, Kyiv, Ukraine, 03022


This review is devoted to the progress made during the last decade towards understanding of basic mechanisms of post-translational protein folding in bacteria. Particular investigation was done on the role of chaperonins, their structure and mechanism of action in facilitating protein folding. The specificity of chaperonins in respect to the existence of multiple genes for chaperonins in some bacteria is discussed.


[1] Anfinsen CB. Principles that govern the folding of protein chains. Science. 1973;181(4096):223-30.
[2] Kim PS, Baldwin RL. Specific intermediates in the folding reactions of small proteins and the mechanism of protein folding. Annu Rev Biochem. 1982;51:459-89. Review.
[3] Jaenicke R. Folding and association of proteins. Prog Biophys Mol Biol. 1987;49(2-3):117-237.
[4] Rietsch A, Belin D, Martin N, Beckwith J. An in vivo pathway for disulfide bond isomerization in Escherichia coli. Proc Natl Acad Sci U S A. 1996;93(23):13048-53.
[5] Pelham HR. Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell. 1986;46(7):959-61.
[6] Gragerov A, Nudler E, Komissarova N, Gaitanaris GA, Gottesman ME, Nikiforov V. Cooperation of GroEL/GroES and DnaK/DnaJ heat shock proteins in preventing protein misfolding in Escherichia coli. Proc Natl Acad Sci U S A. 1992;89(21):10341-4.
[7] Kusukawa N, Yura T. Heat shock protein GroE of Escherichia coli: key protective roles against thermal stress. Genes Dev. 1988;2(7):874-82.
[8] Goloubinoff P, Gatenby AA, Lorimer GH. GroE heat-shock proteins promote assembly of foreign prokaryotic ribulose bisphosphate carboxylase oligomers in Escherichia coli. Nature. 1989;337(6202):44-7.
[9] Goloubinoff P, Christeller JT, Gatenby AA, Lorimer GH. Reconstitution of active dimeric ribulose bisphosphate carboxylase from an unfoleded state depends on two chaperonin proteins and Mg-ATP. Nature. 1989 Dec 21-28;342(6252):884-9.
[10] Hemmingsen SM, Woolford C, van der Vies SM, Tilly K, Dennis DT, Georgopoulos CP, Hendrix RW, Ellis RJ. Homologous plant and bacterial proteins chaperone oligomeric protein assembly. Nature. 1988;333(6171):330-4.
[11] Laskey RA, Honda BM, Mills AD, Finch JT. Nucleosomes are assembled by an acidic protein which binds histones and transfers them to DNA. Nature. 1978;275(5679):416-20.
[12] Horwich AL, Low KB, Fenton WA, Hirshfield IN, Furtak K. Folding in vivo of bacterial cytoplasmic proteins: role of GroEL. Cell. 1993;74(5):909-17.
[13] Mogk A, V?lker A, Engelmann S, Hecker M, Schumann W, V?lker U. Nonnative proteins induce expression of the Bacillus subtilis CIRCE regulon. J Bacteriol. 1998;180(11):2895-900.
[14] Nover JL Inducers of Hsp synthesis: heat shock and chemical stressors. Heat shock responce. Ed. L. Nover. Boca Raton: CPC press, 1991: 5-40.
[15] Gupta RS. Evolutionary relationships of chaperonins. The chaperonins. Ed. R. J. Ellis. New York: Acad, press, 1996: 27-64.
[16] Rospert S, Glick BS, Jen? P, Schatz G, Todd MJ, Lorimer GH, Viitanen PV. Identification and functional analysis of chaperonin 10, the groES homolog from yeast mitochondria. Proc Natl Acad Sci U S A. 1993;90(23):10967-71.
[17] Viitanen PV, Schmidt M, Buchner J, Suzuki T, Vierling E, Dickson R, Lorimer GH, Gatenby A, Soll J. Functional characterization of the higher plant chloroplast chaperonins. J Biol Chem. 1995;270(30):18158-64.
[18] Macario AJ, Lange M, Ahring BK, Conway de Macario E. Stress genes and proteins in the archaea. Microbiol Mol Biol Rev. 1999;63(4):923-67.
[19] Macario AJ, Conway de Macario E. The archaeal molecular chaperone machine: peculiarities and paradoxes. Genetics. 1999;152(4):1277-83.
[20] Tilly K, Murialdo H, Georgopoulos C. Identification of a second Escherichia coli groE gene whose product is necessary for bacteriophage morphogenesis. Proc Natl Acad Sci U S A. 1981;78(3):1629-33.
[21] Fayet O, Ziegelhoffer T, Georgopoulos C. The groES and groEL heat shock gene products of Escherichia coli are essential for bacterial growth at all temperatures. J Bacteriol. 1989;171(3):1379-85.
[22] McLennan N, Masters M. GroE is vital for cell-wall synthesis. Nature. 1998;392(6672):139.
[23] Yerko VN, Lund PA. Gene cpn60-1 coding one of homologous chaperonins in Rhizobiuin leguminosarum is essential for cell life. Biopolym Cell. 1999; 15(6):516-21.
[24] Hendrix RW. Purification and properties of groE, a host protein involved in bacteriophage assembly. J Mol Biol. 1979;129(3):375-92.
[25] Hohn T, Hohn B, Engel A, Wurtz M, Smith PR. Isolation and characterization of the host protein groE involved in bacteriophage lambda assembly. J Mol Biol. 1979;129(3):359-73.
[26] Hutchinson EG, Tichelaar W, Hofhaus G, Weiss H, Leonard KR. Identification and electron microscopic analysis of a chaperonin oligomer from Neurospora crassa mitochondria. EMBO J. 1989;8(5):1485-90.
[27] Chen S, Roseman AM, Hunter AS, Wood SP, Burston SG, Ranson NA, Clarke AR, Saibil HR. Location of a folding protein and shape changes in GroEL-GroES complexes imaged by cryo-electron microscopy. Nature. 1994;371(6494):261-4.
[28] Martin J, Goldie KN, Engel A, Hartl FU. Topology of the morphological domains of the chaperonin GroEL visualized by immuno-electron microscopy. Biol Chem Hoppe Seyler. 1994;375(9):635-9.
[29] Roseman AM, Chen S, White H, Braig K, Saibil HR. The chaperonin ATPase cycle: mechanism of allosteric switching and movements of substrate-binding domains in GroEL. Cell. 1996;87(2):241-51.
[30] Braig K, Otwinowski Z, Hegde R, Boisvert DC, Joachimiak A, Horwich AL, Sigler PB. The crystal structure of the bacterial chaperonin GroEL at 2.8 A. Nature. 1994;371(6498):578-86.
[31] Fenton WA, Kashi Y, Furtak K, Horwich AL. Residues in chaperonin GroEL required for polypeptide binding and release. Nature. 1994;371(6498):614-9.
[32] Langer T, Pfeifer G, Martin J, Baumeister W, Hartl FU. Chaperonin-mediated protein folding: GroES binds to one end of the GroEL cylinder, which accommodates the protein substrate within its central cavity. EMBO J. 1992;11(13):4757-65.
[33] Braig K, Simon M, Furuya F, Hainfeld JF, Horwich AL. A polypeptide bound by the chaperonin groEL is localized within a central cavity. Proc Natl Acad Sci U S A. 1993;90(9):3978-82.
[34] Creighton TE. Protein folding. Ed. W. H. Freeman. New York, 1992: 519-23.
[35] Hammarstr?m P, Persson M, Owenius R, Lindgren M, Carlsson U. Protein substrate binding induces conformational changes in the chaperonin GroEL. A suggested mechanism for unfoldase activity. J Biol Chem. 2000;275(30):22832-8.
[36] Xu Z, Horwich AL, Sigler PB. The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex. Nature. 1997;388(6644):741-50.
[37] Hayer-Hartl MK, Ewalt KL, Hartl FU. On the role of symmetrical and asymmetrical chaperonin complexes in assisted protein folding. Biol Chem. 1999;380(5):531-40.
[38] Landry SJ, Zeilstra-Ryalls J, Fayet O, Georgopoulos C, Gierasch LM. Characterization of a functionally important mobile domain of GroES. Nature. 1993;364(6434):255-8.
[39] Fenton WA, Horwich AL. GroEL-mediated protein folding. Protein Sci. 1997;6(4):743-60.
[40] Bukau B, Horwich AL. The Hsp70 and Hsp60 chaperone machines. Cell. 1998;92(3):351-66.
[41] Horovitz A. Structural aspects of GroEL function. Curr Opin Struct Biol. 1998;8(1):93-100.
[42] Ben-Zvi AP, Chatellier J, Fersht AR, Goloubinoff P. Minimal and optimal mechanisms for GroE-mediated protein folding. Proc Natl Acad Sci U S A. 1998;95(26):15275-80.
[43] Jackson GS, Staniforth RA, Halsall DJ, Atkinson T, Holbrook JJ, Clarke AR, Burston SG. Binding and hydrolysis of nucleotides in the chaperonin catalytic cycle: implications for the mechanism of assisted protein folding. Biochemistry. 1993;32(10):2554-63.
[44] Fisher MT, Yuan X. The rates of commitment to renaturation of rhodanese and glutamine synthetase in the presence of the groE chaperonins. J Biol Chem. 1994;269(47):29598-601.
[45] Martin J, Langer T, Boteva R, Schramel A, Horwich AL, Hartl FU. Chaperonin-mediated protein folding at the surface of groEL through a 'molten globule'-like intermediate. Nature. 1991;352(6330):36-42.
[46] Dubaqui? Y, Looser R, F?nfschilling U, Jen? P, Rospert S. Identification of in vivo substrates of the yeast mitochondrial chaperonins reveals overlapping but non-identical requirement for hsp60 and hsp10. EMBO J. 1998;17(20):5868-76.
[47] Lorimer GH, Todd MJ, Viitanen PV. Chaperonins and protein folding: unity and disunity of mechanisms. Philos Trans R Soc Lond B Biol Sci. 1993;339(1289):297-303; discussion 303-4.
[48] Viitanen PV, Gatenby AA, Lorimer GH. Purified chaperonin 60 (groEL) interacts with the nonnative states of a multitude of Escherichia coli proteins. Protein Sci. 1992;1(3):363-9.
[49] Ellis RJ, Hartl FU. Protein folding in the cell: competing models of chaperonin function. FASEB J. 1996;10(1):20-6.
[50] Lorimer GH. A quantitative assessment of the role of the chaperonin proteins in protein folding in vivo. FASEB J. 1996;10(1):5-9.
[51] Ewalt KL, Hendrick JP, Houry WA, Hartl FU. In vivo observation of polypeptide flux through the bacterial chaperonin system. Cell. 1997;90(3):491-500.
[52] Houry WA, Frishman D, Eckerskorn C, Lottspeich F, Hartl FU. Identification of in vivo substrates of the chaperonin GroEL. Nature. 1999;402(6758):147-54.
[53] Rospert S, Looser R, Dubaquie Y, Matouschek A, Glick BS, Schatz G. Hsp60-independent protein folding in the matrix of yeast mitochondria. EMBO J. 1996;15(4):764-74.
[54] Dubaqui? Y, Looser R, Rospert S. Significance of chaperonin 10-mediated inhibition of ATP hydrolysis by chaperonin 60. Proc Natl Acad Sci U S A. 1997;94(17):9011-6.
[55] Guglielmi G, Mazodier P, Thompson CJ, Davies J. A survey of the heat shock response in four Streptomyces species reveals two groEL-like genes and three groEL-like proteins in Streptomyces albus. J Bacteriol. 1991;173(22):7374-81.
[56] de Le?n P, Marco S, Isiegas C, Marina A, Carrascosa JL, Mellado RP. Streptomyces lividans groES, groEL1 and groEL2 genes. Microbiology. 1997;143 ( Pt 11):3563-71.
[57] Kong TH, Coates AR, Butcher PD, Hickman CJ, Shinnick TM. Mycobacterium tuberculosis expresses two chaperonin-60 homologs. Proc Natl Acad Sci U S A. 1993;90(7):2608-12.
[58] Rusanganwa E, Gupta RS. Cloning and characterization of multiple groEL chaperonin-encoding genes in Rhizobium meliloti. Gene. 1993;126(1):67-75.
[59] Yerko VN, Downie JA, Lund PA. Are the three chaperonin operons of Rhizobium leguminosarum essential?. Current Plant Science and Biotechnology in Agriculture. Biological Nitrogen Fixation for the 21st Century. Eds C. Elmerich, A. Kondorosi, W. E. Newton. Dordrecht; Boston; London: Kluwer Acad, publ., 1998. Vol. 31: 248. ttp://
[60] Babst M, Hennecke H, Fischer HM. Two different mechanisms are involved in the heat-shock regulation of chaperonin gene expression in Bradyrhizobium japonicum. Mol Microbiol. 1996;19(4):827-39.
[61] Yerko VM, Zdorovenko OL, Kovalchuk MV. Mutants Rhizobium leguminosarum bv. phaseoli genes for the synthesis of chaperonines exhibit altered symbiotic properties. Genetics and breeding in Ukraine at the Millennium. Ed VV Morgun. Kiev, 2000. vol. 1: 640-647.
[62] Marusich EI, Kurochkina LP, Mesyanzhinov VV. Chaperones in bacteriophage T4 assembly. Biochemistry (Mosc). 1998;63(4):399-406.
[63] Betancourt MR, Thirumalai D. Exploring the kinetic requirements for enhancement of protein folding rates in the GroEL cavity. J Mol Biol. 1999;287(3):627-44.
[64] Byrne GI, Kalayoglu MV. Chlamydia pneumoniae and atherosclerosis: links to the disease process. Am Heart J. 1999;138(5 Pt 2):S488-90.
[65] Paju S, Goulhen F, Asikainen S, Grenier D, Mayrand D, Uitto V. Localization of heat shock proteins in clinical Actinobacillus actinomycetemcomitans strains and their effects on epithelial cell proliferation. FEMS Microbiol Lett. 2000;182(2):231-5.
[66] Rosenkrands I, Weldingh K, Ravn P, Brandt L, H?jrup P, Rasmussen PB, Coates AR, Singh M, Mascagni P, Andersen P. Differential T-cell recognition of native and recombinant Mycobacterium tuberculosis GroES. Infect Immun. 1999;67(11):5552-8.
[67] LaVerda D, Albanese LN, Ruther PE, Morrison SG, Morrison RP, Ault KA, Byrne GI. Seroreactivity to Chlamydia trachomatis Hsp10 correlates with severity of human genital tract disease. Infect Immun. 2000;68(1):303-9.
[68] Hoffman PS, Garduno RA. Surface-associated heat shock proteins of Legionella pneumophila and Helicobacter pylori: roles in pathogenesis and immunity. Infect Dis Obstet Gynecol. 1999;7(1-2):58-63.
[69] Chua-Intra B, Peerapakorn S, Davey N, Jurcevic S, Busson M, Vordermeier HM, Pirayavaraporn C, Ivanyi J. T-cell recognition of mycobacterial GroES peptides in Thai leprosy patients and contacts. Infect Immun. 1998;66(10):4903-9.
[70] Kong TH, Coates AR, Butcher PD, Hickman CJ, Shinnick TM. Mycobacterium tuberculosis expresses two chaperonin-60 homologs. Proc Natl Acad Sci U S A. 1993;90(7):2608-12.
[71] Zaborina O, Misra N, Kostal J, Kamath S, Kapatral V, El-Idrissi ME, Prabhakar BS, Chakrabarty AM. P2Z-Independent and P2Z receptor-mediated macrophage killing by Pseudomonas aeruginosa isolated from cystic fibrosis patients. Infect Immun. 1999;67(10):5231-42.