1887

Abstract

Heat shock proteins are highly conserved, stress-inducible, ubiquitous proteins that maintain homeostasis in both eukaryotes and prokaryotes. Hsp70 proteins belong to the heat shock protein family and enhance bacterial survival in hostile environments. Hsp70, known as DnaK in prokaryotes, supports numerous processes such as the assembly and disassembly of protein complexes, the refolding of misfolded and clustered proteins, membrane translocation and the regulation of regulatory proteins. The chaperone-based activity of Hsp70 depends on dynamic interactions between its two domains, known as the ATPase domain and the substrate-binding domain. It also depends on interactions between these domains and other co-chaperone molecules such as the Hsp40 protein family member DnaJ and nucleotide exchange factors. DnaJ is the primary chaperone that interacts with nascent polypeptide chains and functions to prevent their premature release from the ribosome and misfolding before it is targeted by DnaK. Adhesion of bacteria to host cells is mediated by both host and bacterial Hsp70. Following infection of the host, bacterial Hsp70 (DnaK) is in a position to initiate bacterial survival processes and trigger an immune response by the host. Any mutations in the gene have been shown to decrease the viability of bacteria inside the host. This review will give insights into the structure and mechanism of Hsp70 and its role in regulating the protein activity that contributes to pathogenesis.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000429
2017-03-01
2020-11-30
Loading full text...

Full text loading...

/deliver/fulltext/jmm/66/3/259.html?itemId=/content/journal/jmm/10.1099/jmm.0.000429&mimeType=html&fmt=ahah

References

  1. Jolly C, Morimoto RI. Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 2000;92:1564–1572 [CrossRef][PubMed]
    [Google Scholar]
  2. Mayer MP, Rüdiger S, Bukau B. Molecular basis for interactions of the DnaK chaperone with substrates. Biol Chem 2000;381:877–885 [CrossRef]
    [Google Scholar]
  3. Hesterkamp T, Bukau B. Role of the DnaK and HscA homologs of Hsp70 chaperones in protein folding in E.coli. EMBO J 1998;17:4818–4828 [CrossRef]
    [Google Scholar]
  4. Schröder H, Langer T, Hartl FU, Bukau B. DnaK, DnaJ and GrpE form a cellular chaperone machinery capable of repairing heat-induced protein damage. EMBO J 1993;12:4137–4144[PubMed]
    [Google Scholar]
  5. Kampinga HH, Craig EA. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol 2010;11:579–592 [CrossRef]
    [Google Scholar]
  6. Evans CG, Chang L, Gestwicki JE. Heat shock protein 70 (hsp70) as an emerging drug target. J Med Chem 2010;53:4585–4602 [CrossRef][PubMed]
    [Google Scholar]
  7. Zylicz M, Wawrzynow A. Insights into the function of Hsp70 chaperones. IUBMB Life 2001;51:283–287 [CrossRef][PubMed]
    [Google Scholar]
  8. Turturici G, Sconzo G, Geraci F. Hsp70 and its molecular role in nervous system diseases. Biochem Res Int 2011;2011:618127 [CrossRef]
    [Google Scholar]
  9. Bertelsen EB, Chang L, Gestwicki JE, Zuiderweg ERP. Solution conformation of wild-type E. coli Hsp70 (DnaK) chaperone complexed with ADP and substrate. Proc Natl Acad Sci USA 2009;106:8471–8476 [CrossRef]
    [Google Scholar]
  10. Zuiderweg ER, Bertelsen EB, Rousaki A, Mayer MP, Gestwicki JE et al. Allostery in the Hsp70 chaperone proteins. Top Curr Chem 2013;328:99–153 [CrossRef][PubMed]
    [Google Scholar]
  11. Morshauser RC, Wang H, Flynn GC, Zuiderweg ERP. The peptide-binding domain of the chaperone protein Hsc70 has an unusual secondary structure topology. Biochemistry 1995;34:6261–6266 [CrossRef][PubMed]
    [Google Scholar]
  12. Kityk R, Kopp J, Sinning I, Mayer MP. Structure and dynamics of the ATP-bound open conformation of Hsp70 chaperones. Mol Cell 2012;48:863–874 [CrossRef][PubMed]
    [Google Scholar]
  13. Mayer MP, Brehmer D, Gässler CS, Bukau B. Hsp70 chaperone machines. Adv Protein Chem 2001;59:1–44[PubMed][CrossRef]
    [Google Scholar]
  14. Caplan AJ. What is a co-chaperone?. Cell Stress Chaperones 2003;8:105–107 [CrossRef]
    [Google Scholar]
  15. Cheetham ME, Caplan AJ. Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function. Cell Stress Chaperones 1998;3:28–36 [CrossRef]
    [Google Scholar]
  16. Mayer MP. Hsp70 chaperone dynamics and molecular mechanism. Trends Biochem Sci 2013;38:507–514 [CrossRef][PubMed]
    [Google Scholar]
  17. Langer T, Lu C, Echols H, Flanagan J, Hayer MK et al. Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding. Nature 1992;356:683–689 [CrossRef][PubMed]
    [Google Scholar]
  18. Ron EZ, Segal G, Sirkis R, Robinson M, Graur D et al. Regulation of heat-shock response in bacteria. Stress genes: role in physiological ecology. In Bell CR, Brylinsky M, Johnson Green P. (editors) Proceedings of the 8th International Symposium on Microbial Ecology Halifax, Canada: Atlanatic Canada Society for microbial Ecology; 2000; pp.649–655
    [Google Scholar]
  19. Silberg JJ, Hoff KG, Vickery LE. The Hsc66-Hsc20 chaperone system in Escherichia coli: chaperone activity and interactions with the DnaK-DnaJ-grpE system. J Bacteriol 1998;180:6617–6624[PubMed]
    [Google Scholar]
  20. Woo HJ, Jiang J, Lafer EM, Sousa R. ATP-induced conformational changes in Hsp70: molecular dynamics and experimental validation of an in silico predicted conformation. Biochemistry 2009;48:11470–11477 [CrossRef][PubMed]
    [Google Scholar]
  21. Lund PA. Molecular Chaperones in the Cell Oxford: Oxford University Press; 2001
    [Google Scholar]
  22. Sekhar A, Rosenzweig R, Bouvignies G, Kay L. Mapping the conformation of a client protein through the Hsp70 functional cycle. Proc Natl Acad Sci USA 2015;112:10395–10400 [CrossRef][PubMed]
    [Google Scholar]
  23. Bukau B, Horwich AL. The Hsp70 and Hsp60 chaperone machines. Cell 1998;92:351–366 [CrossRef][PubMed]
    [Google Scholar]
  24. Fink AL. Chaperone-mediated protein folding. Physiol Rev 1999;79:425–449[PubMed]
    [Google Scholar]
  25. Teter SA, Houry WA, Ang D, Tradler T, Rockabrand D et al. Polypeptide flux through bacterial Hsp70: DnaK cooperates with trigger factor in chaperoning nascent chains. Cell 1999;97:755–765[PubMed][CrossRef]
    [Google Scholar]
  26. Segal G, Ron EZ. Regulation of heat-shock response in bacteria. Ann N Y Acad Sci 1998;851:147–151 [CrossRef][PubMed]
    [Google Scholar]
  27. Maleki F, Khosravi A, Nasser A, Taghinejad H, Azizian M. Bacterial heat shock protein activity. J Clin Diagn Res 2016;10:BE01–BE03 [CrossRef][PubMed]
    [Google Scholar]
  28. Zhang H, Yang J, Wu S, Gong W, Chen C et al. Glutathionylation of the bacterial Hsp70 chaperone DnaK provides a link between oxidative stress and the heat shock response. J Biol Chem 2016;291:6967–6981 [CrossRef][PubMed]
    [Google Scholar]
  29. Nonaka G, Blankschien M, Herman C, Gross CA, Rhodius VA. Regulon and promoter analysis of the E. coli heat-shock factor, σ32, reveals a multifaceted cellular response to heat stress. Genes Dev 2006;20:1776–1789 [CrossRef][PubMed]
    [Google Scholar]
  30. Henderson B, Allan E, Coates AR, Wars S. Stress wars: the direct role of host and bacterial molecular chaperones in bacterial infection. Infect Immun 2006;74:3693–3706 [CrossRef]
    [Google Scholar]
  31. Chatterjee I, Becker P, Grundmeier M, Bischoff M, Somerville GA et al. Staphylococcus aureus ClpC is required for stress resistance, aconitase activity, growth recovery, and death. J Bacteriol 2005;187:4488–4496 [CrossRef][PubMed]
    [Google Scholar]
  32. Vanghele M, Ganea E. The role of bacterial molecular chaperones in pathogen survival within the host. Rom J Biochem 2010;47:87–100
    [Google Scholar]
  33. Huesca M, Goodwin A, Bhagwansingh A, Hoffman P, Lingwood CA. Characterization of an acidic-pH-inducible stress protein (hsp70), a putative sulfatide binding adhesin, from Helicobacter pylori. Infect Immun 1998;66:4061–4067[PubMed]
    [Google Scholar]
  34. Takaya A, Tomoyasu T, Matsui H, Yamamoto T. The DnaK/DnaJ chaperone machinery of Salmonella enterica serovar Typhimurium is essential for invasion of epithelial cells and survival within macrophages, leading to systemic infection. Infect Immun 2004;72:1364–1373 [CrossRef][PubMed]
    [Google Scholar]
  35. Genevaux P, Keppel F, Schwager F, Langendijk-Genevaux PS, Hartl FU et al. In vivo analysis of the overlapping functions of DnaK and trigger factor. EMBO Rep 2004;5:195–200 [CrossRef][PubMed]
    [Google Scholar]
  36. Sikora A, Grzesiuk E. Heat shock response in gastrointestinal tract. J Physiol Pharmacol 2007;58:43–62[PubMed]
    [Google Scholar]
  37. Neckers L, Tatu U. Molecular chaperones in pathogen virulence: emerging new targets for therapy. Cell Host Microbe 2008;4:519–527 [CrossRef]
    [Google Scholar]
  38. Kohler S, Ekaza E, Paquet J-Y, Walravens K, Teyssier J et al. Induction of dnaK through its native heat shock promoter is necessary for intramacrophagic replication of Brucella suis. Infect Immun 2002;70:1631–1634 [CrossRef][PubMed]
    [Google Scholar]
  39. Kaufmann SHE. Heat-shock proteins and pathogenesis of bacterial infections. Springer Semin Immunopathol 1991;13:25–36 [CrossRef][PubMed]
    [Google Scholar]
  40. Barbatis C, Tsopanomichalou M. Heat shock proteins in inflammatory bowel disease. Ann Gastroenterol 2009;22:244–247
    [Google Scholar]
  41. Samborski P, Grzymisławski M. The role of HSP70 heat shock proteins in the pathogenesis and treatment of inflammatory bowel diseases. Adv Clin Exp Med 2015;24:525–530 [CrossRef][PubMed]
    [Google Scholar]
  42. Retzlaff C, Yamamoto Y, Hoffman PS, Friedman H, Klein TW. Bacterial heat shock proteins directly induce cytokine mRNA and interleukin-1 secretion in macrophage cultures. Infect Immun 1994;62:5689–5693[PubMed]
    [Google Scholar]
  43. Das Gupta T, Bandyopadhyay B, Das Gupta SK. Modulation of DNA-binding activity of Mycobacterium tuberculosis HspR by chaperones. Microbiology 2008;154:484–490 [CrossRef][PubMed]
    [Google Scholar]
  44. Bleotu C, Chifiriuc MC, Pircalabioru G, Berteşteanu SVG, Grigore R et al. Significance of serum antibodies against HSP 60 and HSP 70 for the diagnostic of infectious diseases. Virulence 2014;5:828–831 [CrossRef][PubMed]
    [Google Scholar]
  45. Chiappori F, Fumian M, Milanesi L, Merelli I. DnaK as antibiotic target: hot spot residues analysis for differential inhibition of the bacterial protein in comparison with the human HSP70. PLoS One 2015;10:e0124563 [CrossRef][PubMed]
    [Google Scholar]
  46. Singh V, Utaida S, Jackson L, Jayaswal R, Wilkinson B et al. Role for dnaK locus in tolerance of multiple stresses in Staphylococcus aureus. Microbiology 2007;153:3162–3173 [CrossRef][PubMed]
    [Google Scholar]
  47. Yamaguchi Y, Tomoyasu T, Takaya A, Morioka M, Yamamoto T. Effect of disruption of heat shock genes on susceptibility of Escherichia coli to fluoroquinolones. BMC Microbiol 2033;3:16[CrossRef]
    [Google Scholar]
  48. Patury S, Miyata Y, Gestwicki JE. Pharmacological targeting of the Hsp70 chaperone. Curr Top Med Chem 2009;9:1337–1351 [CrossRef][PubMed]
    [Google Scholar]
  49. Horváth I, Multhoff G, Sonnleitner A, Vígh L et al. Membrane-associated stress proteins: more than simply chaperones. Biochim Biophys Acta 2008;1778:1653–1664 [CrossRef]
    [Google Scholar]
  50. Jeffery CJ. Moonlighting proteins. Trends Biochem Sci 1999;24:8–11 [CrossRef][PubMed]
    [Google Scholar]
  51. Henderson B, Martin A. Bacterial moonlighting proteins and bacterial virulence. Curr Top Microbiol Immunol 2013;358:155–213 [CrossRef][PubMed]
    [Google Scholar]
  52. Knaust A, Weber MV, Hammerschmidt S, Bergmann S, Frosch M et al. Cytosolic proteins contribute to surface plasminogen recruitment of Neisseria meningitidis. J Bacteriol 2007;189:3246–3255 [CrossRef][PubMed]
    [Google Scholar]
  53. Candela M, Centanni M, Fiori J, Biagi E, Turroni S et al. DnaK from Bifidobacterium animalis subsp. lactis is a surface-exposed human plasminogen receptor upregulated in response to bile salts. Microbiology 2010;156:1609–1618 [CrossRef][PubMed]
    [Google Scholar]
  54. Lehner T, Bergmeier LA, Wang Y, Tao L, Sing M et al. Heat shock proteins generate beta-chemokines which function as innate adjuvants enhancing adaptive immunity. Eur J Immunol 2000;30:594–603 [CrossRef][PubMed]
    [Google Scholar]
  55. Wang Y, Kelly C, Karttunen JT, Whittall T, Lehner PJ et al. CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines. Immunity 2001;15:971–983 [CrossRef][PubMed]
    [Google Scholar]
  56. Whittall T, Wang Y, Younson J, Kelly C, Bergmeier L et al. Interaction between the CCR5 chemokine receptors and microbial HSP70. Eur J Immunol 2006;36:2304–2314 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000429
Loading
/content/journal/jmm/10.1099/jmm.0.000429
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error