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Gene Review

dnaK  -  molecular chaperone DnaK

Escherichia coli O157:H7 str. Sakai

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Disease relevance of dnaK


High impact information on dnaK

  • Cell survival under severe thermal stress requires the activity of the ClpB (Hsp104) AAA+ chaperone that solubilizes and reactivates aggregated proteins in concert with the DnaK (Hsp70) chaperone system [6].
  • A role for DnaK, the major E. coli Hsp70, in chaperoning de novo protein folding has remained elusive [7].
  • Genetic evidence indicates central roles for Hsp70 chaperones in the regulation of heat shock gene expression [8].
  • The dnaK protein modulates the heat-shock response of Escherichia coli [1].
  • Addition of Mg-ATP results in the dissociation of the substrate polypeptides from the chaperone, but as ATP-gamma S (an ATP analogue that is only slowly hydrolysable) cannot substitute for ATP in this reaction, it has been concluded that ATP hydrolysis is necessary to dissociate Hsp70-substrate protein complexes [9].

Chemical compound and disease context of dnaK

  • NH2-terminal sequence analysis revealed the 72-kDa protein to have 100% identity with the first 13 amino acid residues of the Escherichia coli dnaK heat shock protein [10].
  • In vivo, elevated proline pools in Escherichia coli (obtained by altering the feedback inhibition by proline of gamma-glutamylkinase, the first enzyme of the proline biosynthesis pathway) restore the viability of a dnaK-deficient mutant at 42 degrees C, suggesting that proline can act as a thermoprotectant for E. coli cells [11].
  • The product of the dnaK gene has been identified on SDS polyacrylamide gels after infection of UV-irradiated E. coli cells [12].
  • When the A6-d-ANase gene was expressed in the Escherichia coli dnaK mutant dnaK756, little activity was observed in the soluble fraction, and it was restored by the coexpression of DnaKJE or the substitution of the R354 residue of A6-d-ANase for lysine [13].
  • 5. The chemical analysis of the phosphorylated moiety of dnaK protein showed that it was modified exclusively at serine residues during normal growth of cells, and mostly at threonine residues after phage infection [14].

Biological context of dnaK


Anatomical context of dnaK

  • The fusion protein, which co-purifies with the bacterial chaperones dnaK and groEL, binds to glyoxysomes and is partially translocated in an ATP-dependent reaction which is independent of eukaryotic cytosol [18].
  • These abnormal ribosomal particles are rescued if the mutant cells are returned to 30 degrees C. Thus, the product of the dnaK gene is implicated in ribosome biogenesis at high temperature [19].
  • These enzymes were synthesized mostly in soluble, fully enzymatically active forms in wild-type E. coli cells cultured in the temperature range 20-42 degrees C, but aggregated extensively in dnaK null mutants [20].
  • Using non-pathogenic Escherichia coli strains and the human monocytic cell line U937, we showed that deletion of the dnaK gene significantly increased the rate of initial intracellular killing of bacteria [21].
  • Immediately after phagocytosis, the number of viable dnaK mutant bacteria found within macrophages was significantly lower compared to that of intracellular wild type bacteria [22].

Associations of dnaK with chemical compounds

  • We analyzed the effects of dnaK mutations which alter the corresponding glutamate-171 of DnaK to alanine, leucine or lysine [23].
  • In addition, after incubating cells with [32P]orthophosphate at 42 degrees C, the 32P-labeled dnaK bound quantitatively to the CRAG column, unlike the nonlabeled protein [24].
  • The chemical chaperone proline relieves the thermosensitivity of a dnaK deletion mutant at 42 degrees C [11].
  • In the presence of stress, heat or ethanol (4%), the X. campestris pv. campestris 17 grpE and dnaK promoters were induced two- to three-fold over controls [25].
  • The NH2-terminal sequence of this protein and the internal sequences of the tryptic peptides covering 1/3 of the total number of residues coincided with that deduced from the nucleotide sequence of the dnaK gene isolated from H. cutirubrum [26].

Regulatory relationships of dnaK


Other interactions of dnaK

  • First step of this disassembling reaction is the binding of dnaK protein to lambda P protein [28].
  • While dnaK and tig are the essential components for nascent polypeptide folding in E. coli, deletion did not confer synthetic lethality in B. subtilis, suggesting that under normal growth conditions, another system or mechanism with a specific role prevails [29].
  • Steady-state experiments revealed that Hsc66 has a low affinity for ATP (K(m)(ATP) = 12.7 microM) compared with other hsp70 chaperones [27].
  • Heat stress at 42.5 degrees C appeared to be the optimum temperature for HSP formation in cells grown at 30 degrees C. The relative rate of synthesis of HSP70 and HSP15 reached a maximum at 30 min after the temperature shift-up whereas the capability of cells to accumulate HSP64 and HSP14 continued through 2 h [30].
  • Hsc66, a stress-70 protein, and Hsc20, a J-type accessory protein, comprise a newly described Hsp70-type chaperone system in addition to DnaK-DnaJ-GrpE in Escherichia coli [31].

Analytical, diagnostic and therapeutic context of dnaK

  • This modification appears to be phosphorylation; after treatment with phosphatases, the ATP-eluted dnaK resembled the predominant form in electrophoretic and binding properties [24].
  • The DnaK epitope was determined by Western blot analysis of a series of truncated DnaK fragments overproduced in Escherichia coli using 5' and 3' dnaK-deleted expression plasmids [32].
  • A fragment of the dnaK gene was amplified from these strains by PCR with oligonucleotide primers targeting regions of the dnaK gene that are conserved at the amino acid level, and the resulting PCR products were cloned into a plasmid vector [33].
  • Furthermore, analysis of aggregated proteins in the dnaK-deficient strain at 42 degrees C by two-dimensional gel electrophoresis shows that high proline pools reduce the protein aggregation defect of the dnaK-deficient strain [11].
  • The results of HspR titration experiments, where the dnaK operon promoter region was cloned at ca. 50 copies per chromosome, were consistent with the prediction that HspR functions as a negative autoregulator [34].


  1. The dnaK protein modulates the heat-shock response of Escherichia coli. Tilly, K., McKittrick, N., Zylicz, M., Georgopoulos, C. Cell (1983) [Pubmed]
  2. The dnaK protein of Escherichia coli possesses an ATPase and autophosphorylating activity and is essential in an in vitro DNA replication system. Zylicz, M., LeBowitz, J.H., McMacken, R., Georgopoulos, C. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  3. Purification and properties of the Escherichia coli dnaK replication protein. Zylicz, M., Georgopoulos, C. J. Biol. Chem. (1984) [Pubmed]
  4. Post-transcriptional regulation of the Bacillus subtilis dnaK operon. Homuth, G., Mogk, A., Schumann, W. Mol. Microbiol. (1999) [Pubmed]
  5. Nucleotide sequence of a Bacillus megaterium gene homologous to the dnaK gene of Escherichia coli. Sussman, M.D., Setlow, P. Nucleic Acids Res. (1987) [Pubmed]
  6. Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB. Weibezahn, J., Tessarz, P., Schlieker, C., Zahn, R., Maglica, Z., Lee, S., Zentgraf, H., Weber-Ban, E.U., Dougan, D.A., Tsai, F.T., Mogk, A., Bukau, B. Cell (2004) [Pubmed]
  7. Polypeptide flux through bacterial Hsp70: DnaK cooperates with trigger factor in chaperoning nascent chains. Teter, S.A., Houry, W.A., Ang, D., Tradler, T., Rockabrand, D., Fischer, G., Blum, P., Georgopoulos, C., Hartl, F.U. Cell (1999) [Pubmed]
  8. Physical interaction between heat shock proteins DnaK, DnaJ, and GrpE and the bacterial heat shock transcription factor sigma 32. Gamer, J., Bujard, H., Bukau, B. Cell (1992) [Pubmed]
  9. ATP-induced protein-Hsp70 complex dissociation requires K+ but not ATP hydrolysis. Palleros, D.R., Reid, K.L., Shi, L., Welch, W.J., Fink, A.L. Nature (1993) [Pubmed]
  10. Characterization of antigenic determinants of Borrelia burgdorferi shared by other bacteria. Coleman, J.L., Benach, J.L. J. Infect. Dis. (1992) [Pubmed]
  11. The chemical chaperone proline relieves the thermosensitivity of a dnaK deletion mutant at 42 degrees C. Chattopadhyay, M.K., Kern, R., Mistou, M.Y., Dandekar, A.M., Uratsu, S.L., Richarme, G. J. Bacteriol. (2004) [Pubmed]
  12. Identification of the C. coli dnaK (groPC756) gene product. Georgopoulos, C.P., Lam, B., Lundquist-Heil, A., Rudolph, C.F., Yochem, J., Feiss, M. Mol. Gen. Genet. (1979) [Pubmed]
  13. Site-directed mutagenesis alters DnaK-dependent folding process. Yoshimune, K., Esaki, N., Moriguchi, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  14. Effect of bacteriophage M13 infection on phosphorylation of dnaK protein and other Escherichia coli proteins. Rieul, C., Cortay, J.C., Bleicher, F., Cozzone, A.J. Eur. J. Biochem. (1987) [Pubmed]
  15. Initiation of lambda DNA replication with purified host- and bacteriophage-encoded proteins: the role of the dnaK, dnaJ and grpE heat shock proteins. Zylicz, M., Ang, D., Liberek, K., Georgopoulos, C. EMBO J. (1989) [Pubmed]
  16. Consensus sequence for Escherichia coli heat shock gene promoters. Cowing, D.W., Bardwell, J.C., Craig, E.A., Woolford, C., Hendrix, R.W., Gross, C.A. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  17. Major heat shock gene of Drosophila and the Escherichia coli heat-inducible dnaK gene are homologous. Bardwell, J.C., Craig, E.A. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  18. Characterization of intermediates in the process of plant peroxisomal protein import. Pool, M.R., López-Huertas, E., Baker, A. EMBO J. (1998) [Pubmed]
  19. Mutant DnaK chaperones cause ribosome assembly defects in Escherichia coli. Alix, J.H., Guérin, M.F. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  20. The 70-kDa heat-shock protein/DnaK chaperone system is required for the productive folding of ribulose-biphosphate carboxylase subunits in Escherichia coli. Checa, S.K., Viale, A.M. Eur. J. Biochem. (1997) [Pubmed]
  21. Complementation of a DnaK-deficient Escherichia coli strain with the dnaK/dnaJ operon of Brucella ovis reduces the rate of initial intracellular killing within the monocytic cell line U937. Caron, E., Cellier, M., Liautard, J.P., Köhler, S. FEMS Microbiol. Lett. (1994) [Pubmed]
  22. The Listeria monocytogenes DnaK chaperone is required for stress tolerance and efficient phagocytosis with macrophages. Hanawa, T., Fukuda, M., Kawakami, H., Hirano, H., Kamiya, S., Yamamoto, T. Cell Stress Chaperones (1999) [Pubmed]
  23. The chaperone function of DnaK requires the coupling of ATPase activity with substrate binding through residue E171. Buchberger, A., Valencia, A., McMacken, R., Sander, C., Bukau, B. EMBO J. (1994) [Pubmed]
  24. Heat shock of Escherichia coli increases binding of dnaK (the hsp70 homolog) to polypeptides by promoting its phosphorylation. Sherman, M.Y., Goldberg, A.L. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  25. Characterization of stress-responsive genes, hrcA-grpE-dnaK-dnaJ, from phytopathogenic Xanthomonas campestris. Weng, S.F., Tai, P.M., Yang, C.H., Wu, C.D., Tsai, W.J., Lin, J.W., Tseng, Y.H. Arch. Microbiol. (2001) [Pubmed]
  26. Identification and partial purification of DnaK homologue from extremely halophilic archaebacteria, Halobacterium cutirubrum. Tokunaga, H., Hara, S., Arakawa, T., Ishibashi, M., Gupta, R.S., Tokunaga, M. J. Protein Chem. (1999) [Pubmed]
  27. Kinetic characterization of the ATPase cycle of the molecular chaperone Hsc66 from Escherichia coli. Silberg, J.J., Vickery, L.E. J. Biol. Chem. (2000) [Pubmed]
  28. Role of the Escherichia coli grpE heat shock protein in the initiation of bacteriophage lambda DNA replication. Osipiuk, J., Zylicz, M. Acta Biochim. Pol. (1991) [Pubmed]
  29. DnaK chaperone machine and trigger factor are only partially required for normal growth of Bacillus subtilis. Reyes, D.Y., Yoshikawa, H. Biosci. Biotechnol. Biochem. (2002) [Pubmed]
  30. Heat shock protein synthesis of the cyanobacterium Synechocystis PCC 6803: purification of the GroEL-related chaperonin. Lehel, C., Wada, H., Kovács, E., Török, Z., Gombos, Z., Horváth, I., Murata, N., Vigh, L. Plant Mol. Biol. (1992) [Pubmed]
  31. The Hsc66-Hsc20 chaperone system in Escherichia coli: chaperone activity and interactions with the DnaK-DnaJ-grpE system. Silberg, J.J., Hoff, K.G., Vickery, L.E. J. Bacteriol. (1998) [Pubmed]
  32. Monoclonal antibody recognition and function of a DnaK (HSP70) epitope found in gram-negative bacteria. Krska, J., Elthon, T., Blum, P. J. Bacteriol. (1993) [Pubmed]
  33. The presence of a dnaK (HSP70) multigene family in members of the orders Planctomycetales and Verrucomicrobiales. Ward-Rainey, N., Rainey, F.A., Stackebrandt, E. J. Bacteriol. (1997) [Pubmed]
  34. Regulation of the dnaK operon of Streptomyces coelicolor A3(2) is governed by HspR, an autoregulatory repressor protein. Bucca, G., Hindle, Z., Smith, C.P. J. Bacteriol. (1997) [Pubmed]
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