Skip to main content
SpringerLink
Log in

Hop: An Hsp70/Hsp90 Co-Chaperone That Functions Within and Beyond Hsp70/Hsp90 Protein Folding Pathways

  • Chapter
Networking of Chaperones by Co-Chaperones

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

Molecular chaperones and their co-chaperones are crucial for the facilitation of efficient protein folding, and prevention of denaturation and aggregation of nascent polypeptides. Hsp70/Hsp90 organizing protein (Hop), a co-chaperone of the two major molecular chaperones, heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90), facilitates their interaction by acting as an adaptor between the two chaperones, so that substrate is efficiently transferred from Hsp70 to Hsp90. Although initial studies reported its scaffolding properties to be its primary function, recent findings suggest an additional modulatory effect of Hop on the activities of Hsp70 and Hsp90. In addition, a more diverse role of Hop, involving structurally and functionally unrelated biomolecules and complexes, is currently being revealed. This review focuses on the integratory and modulatory effects of Hop on the Hsp70 and Hsp90 protein folding pathways, and puts forward evidence and theories regarding its multifaceted roles within various biological systems.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Smith DF, Whitesell L, Katsanis E. Molecular chaperones: Biology and prospects for pharmacological intervention. Pharmacol Rev 1998; 50:493–513.

    CAS  PubMed  Google Scholar 

  2. Morimoto RI. Regulation of the heat shock transcriptional response: Cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 1998; 12:3788–3796.

    Article  CAS  PubMed  Google Scholar 

  3. Frydman J. Folding of newly translated proteins in vivo: The role of molecular chaperones. Annu Rev Biochem 2001; 70:603–647.

    Article  CAS  PubMed  Google Scholar 

  4. Macario AJL, de Macario EC. The archaeal molecular chaperone machine: Peculiarities and paradoxes. Genetics 1999; 152:1277–1283.

    CAS  PubMed  Google Scholar 

  5. Bukau B, Deuerling E, Pfund C et al. Getting newly synthesized proteins into shape. Cell 2000; 101:119–122.

    Article  CAS  PubMed  Google Scholar 

  6. Ryan MT, Pfanner N. Hsp70 proteins in protein translocation. Adv Protein Chem 2001; 59:223–242.

    Article  CAS  PubMed  Google Scholar 

  7. Hard FU, Hayer-Hartl M. Molecular chaperones in the cytosol: From nascent chain to folded protein. Science 2002; 295:1852–1858.

    Article  Google Scholar 

  8. Fink AL. Chaperone-mediated protein folding. Physiol Rev 1999; 79:425–449.

    CAS  PubMed  Google Scholar 

  9. Mayer MP, Schroder H, Rudiger S et al. Multistep mechanism of substrate binding determines chaperone activity of Hsp70. Nat Struct Biol 2000; 7:586–593.

    Article  CAS  PubMed  Google Scholar 

  10. Liberek K, Marszalek J, Ang D et al. Escherichia coli Dnaj and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proc Natl Acad Sci USA 1991; 88:2874–2878.

    Article  CAS  PubMed  Google Scholar 

  11. Sondermann H, Scheufler C, Schneider C et al. Structure of a Bag/Hsc70 complex: Convergent functional evolution of Hsp70 nucleotide exchange factors. Science 2001; 291:1553–1557.

    Article  CAS  PubMed  Google Scholar 

  12. Hohfeld J, Minami Y, Hard FU. Hip, a novel co-chaperone involved in the eukaryotic Hsc70/ Hsp40 reaction cycle. Cell 1995; 83:589–598.

    Article  CAS  PubMed  Google Scholar 

  13. Csermely P, Schnaider T, Söti C et al. The 90-kDa molecular chaperone family: Structure, function, and clinical applications. A comprehensive review. Pharmacol Ther 1998; 79:129–168.

    Article  CAS  PubMed  Google Scholar 

  14. Louvion JF, Abbas-Terki T, Picard D. Hsp90 is required for pheromone signaling in yeast. Mol Biol Cell 1998; 9:3071–3083.

    CAS  PubMed  Google Scholar 

  15. Pratt WB, Toft DO. Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 1997; 18:306–360.

    Article  CAS  PubMed  Google Scholar 

  16. Pratt WB. The role of hsp90-based chaperone system in signal transduction by nuclear receptors and receptors signaling via MAP kinase. Annu Rev Pharmacol Toxicol 1997; 37:297–326.

    Article  CAS  PubMed  Google Scholar 

  17. Panaretou B, Prodromou C, Roe SM et al. ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo. EMBO J 1998; 17:4829–4836.

    Article  CAS  PubMed  Google Scholar 

  18. Zhao R, Davey M, Hsu YC et al. Navigating the chaperone network: An integrative map of physical and genetic interactions mediated by the Hsp90 chaperone. Cell 2005; 120:715–727.

    Article  CAS  PubMed  Google Scholar 

  19. Abbas-Terki T, Donzé O, Briand PA et al. Hspl04 interacts with Hsp90 co-chaperones in respiring yeast. Mol Cell Biol 2001; 21:7569–7575.

    Article  CAS  PubMed  Google Scholar 

  20. Csermely P, Kahn CR. The 90-kDa heat shock protein (hsp-90) possesses an ATP binding site and autophosphorylating activity. J Biol Chem 1991; 266:4943–4950.

    CAS  PubMed  Google Scholar 

  21. Young JC, Hard FU. Polypeptide release by Hsp90 involves ATP hydrolysis and is enhanced by the co-chaperone p23. EMBO J 2000; 19:5930–5940.

    Article  CAS  PubMed  Google Scholar 

  22. Csermely P, Kájtar J, Hollósi M et al. ATP induces a conformational change of the 90-kDa heat shock protein (hsp90). J Biol Chem 1993; 268:1901–1907.

    CAS  PubMed  Google Scholar 

  23. Söti C, Rácz A, Csermely P. A nucleotide-dependent molecular switch controls ATP binding at the C-terminal domain of Hsp90. J Biol Chem 2002; 277:7066–7075.

    Article  PubMed  Google Scholar 

  24. Siligardi G, Panaretou B, Meyer P et al. Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37. J Biol Chem 2002; 277:20151–20159.

    Article  CAS  PubMed  Google Scholar 

  25. Panaretou B, Siligardi G, Meyer P et al. Activation of the ATPase activity of Hsp90 by the stress-regulated co-chaperone Ahal. Mol Cell 2002; 10:1307–1318.

    Article  CAS  PubMed  Google Scholar 

  26. Nicolet CM, Craig EA. Isolation and characterization of STI1, a stress-inducible gene from Saccharomyces cerevisiae. Mol Cell Biol 1989; 9:3638–3646.

    CAS  PubMed  Google Scholar 

  27. Smith DF, Sullivan WP, Marion TN et al. Identification of a 60-kilodalton stress-related protein, p60, which interacts with hsp90 and hsp70. Mol Cell Biol 1993; 13:869–876.

    CAS  PubMed  Google Scholar 

  28. Dittmar KD, Hutchison KA, Owens-Grillo JK et al. Reconstitution of the steroid receptor.hsp90 hetereocomplex assembly system of rabbit reticulocyte lysate. J Biol Chem 1996; 271:12833–12839.

    Article  CAS  PubMed  Google Scholar 

  29. Honoré B, Leffers H, Madsen P et al. Molecular cloning and expression of a transformation-sensitive human protein containing the TPR motif and sharing identity to the stress-inducible yeast protein STI1. J Biol Chem 1992; 267:8485–8491.

    PubMed  Google Scholar 

  30. Blatch GL, Lassie M, Zetter BR et al. Isolation of a mouse cDNA encoding mSTIl, a stress-inducible protein containing the TPR motif. Gene 1997; 194:277–282.

    Article  CAS  PubMed  Google Scholar 

  31. Demand J, Luders J, Hohfeld J. The carboxyl-terminal domain of Hsc70 provides binding sites for a distinct set of chaperone cofactors. Mol Cell Biol 1998; 18:2023–2028.

    CAS  PubMed  Google Scholar 

  32. Adams MD, Celniker SE, Holt RA et al. The genome sequence of Drosophila melanogaster. Science 2000; 287:2185–2195.

    Article  PubMed  Google Scholar 

  33. Zhang Z, Quick MK, Kanelakis KC et al. Characterization of a plant homolog of Hop, a co-chaperone of Hsp90. Plant Physiol 2003; 131:525–535.

    Article  CAS  PubMed  Google Scholar 

  34. Webb JR, Campos-Neto A, Skeiky YAW et al. Molecular characterization of the heat-inducible LmSTIl protein of Leishmania major. Mol Biochem Parasitol 1997; 89:179–193.

    Article  CAS  PubMed  Google Scholar 

  35. Blatch GL, Lassie M. The tetratricopeptide repeat: A structural motif mediating protein-protein interactions. BioEssays 1999; 21:932–939.

    Article  CAS  PubMed  Google Scholar 

  36. van der Spuy J, Kana BD, Dirr HW et al. Heat shock cognate protein 70 chaperone-binding site in the co-chaperone murine stress-inducible protein 1 maps to within three consecutive tetratricopeptide repeat motifs. Biochem J 2000; 345:645–651.

    Article  Google Scholar 

  37. Chen S, Prapapanich V, Rimerman RA et al. Interactions of p60, a mediator of progesterone receptor assembly, with heat shock proteins Hsp90 and Hsp70. Mol Endocrinol 1996; 10:682–693.

    Article  CAS  PubMed  Google Scholar 

  38. Odunuga OO, Hornby JA, Bies C et al. Tetratricopeptide repeat motif-mediated Hsc70-mSTI1 interaction: Molecular characterization of the critical contacts for successful binding and specificity. J Biol Chem 2003; 278:6896–6904.

    Article  CAS  PubMed  Google Scholar 

  39. Brinker A, Scheufler C, von der Mtilbe F et al. Ligand discrimination by TPR domains: Relevance and selectivity of EEVD-recognition in Hsp70.Hop.Hsp90 complexes. J Biol Chem 2002; 277:19265–19275.

    Article  CAS  PubMed  Google Scholar 

  40. Schumacher RJ, Hurst R, Sullivan WP et al. ATP-dependent chaperoning activity of reticulocyte lysate. J Biol Chem 1994; 269:9493–9499.

    CAS  PubMed  Google Scholar 

  41. Lässie M, Blatch GL, Kundra V et al. Stress-inducible murine protein mSTI1: Characterization of binding domains for heat shock proteins and in vitro phosphorylation by different kinases. J Biol Chem 1997; 272:1876–1884.

    Article  Google Scholar 

  42. Hernandez MP, Sullivan WP, Toft DO. The assembly and intermolecular properties of the hsp70-Hop-hsp90 molecular chaperone complex. J Biol Chem 2002; 277:38294–38304.

    Article  CAS  PubMed  Google Scholar 

  43. Scherrer LC, Dalman FC, Massa E et al. Structural and functional reconstitution of the glucocorticoid receptor-Hsp90 complex. J Biol Chem 1990; 265:21397–21400.

    CAS  PubMed  Google Scholar 

  44. Smith DF, Whitesell L, Nair SC et al. Progesterone receptor structure and function altered by geldanamycin, an hsp90-binding agent. Mol Cell Biol 1995; 15:6804–6812.

    CAS  PubMed  Google Scholar 

  45. Chen S, Smith DF. Hop as an adaptor in the heat shock protein 70 (Hsp70) and Hsp90 chaperone machinery. J Biol Chem 1998; 273:35194–35200.

    Article  CAS  PubMed  Google Scholar 

  46. Smith DF, Toft DO. Steroid receptors and their associated proteins. Mol Endocrinol 1993; 7:4–11.

    Article  CAS  PubMed  Google Scholar 

  47. Song Y, Masison DC. Independent regulation of Hsp70 and Hsp90 chaperones by Hsp70/90 organizing protein Stil (Hopl). J Biol Chem 2005; 280:34178–34185.

    Article  CAS  PubMed  Google Scholar 

  48. Wegele H, Müller L, Buchner J. Hsp70 and Hsp90— a relay team for protein folding. Rev Physiol Biochem Pharmacol 2004; 151:1–44.

    Article  CAS  PubMed  Google Scholar 

  49. Murphy PJM, Kanelakis KC, Galigniana MD et al. Stoichiometry, abundance, and functional significance of the hsp90/hsp70-based multiprotein chaperone machinery in reticulocyte lysate. J Biol Chem 2001; 276:30092–30098.

    Article  CAS  PubMed  Google Scholar 

  50. Carrigan PE, Nelson GM, Roberts PJ et al. Multiple domains of the co-chaperone Hop are important for Hsp70 binding. J Biol Chem 2004; 279:16185–16193.

    Article  CAS  PubMed  Google Scholar 

  51. Chang HCJ, Lindquist S. Conservation of Hsp90 macromolecular complexes in Saccharomyces cerevisiae. J Biol Chem 1994; 269:24983–24988.

    CAS  PubMed  Google Scholar 

  52. Chang HCJ, Nathan DF, Lindquist S. In vivo analysis of the Hsp90 co-chaperone Stil (p60). Mol Cell Biol 1997; 17:318–325.

    CAS  PubMed  Google Scholar 

  53. Morishima Y, Kanelakis KC, Silverstein AM et al. The Hsp organizer protein Hop enhances the rate of but is not essential for glucocorticoid receptor folding by the multiprotein Hsp90-based chaperone system. J Biol Chem 2000; 275:6894–6900.

    Article  CAS  PubMed  Google Scholar 

  54. Sullivan W, Stensgard B, Caucutt G et al. Nucleotides and two functional states of hsp90. J Biol Chem 1997; 272:8007–8012.

    Article  CAS  PubMed  Google Scholar 

  55. McLaughlin SH, Smith HW, Jackson SE. Stimulation of the weak ATPase activity of human Hsp90 by a client protein. J Mol Biol 2002; 315:787–798.

    Article  CAS  PubMed  Google Scholar 

  56. Wegele H, Haslbeck M, Reinstein J et al. Stil is a novel activator of the Ssa proteins. J Biol Chem 2003; 278:25970–25976.

    Article  CAS  PubMed  Google Scholar 

  57. Richter K, Muschler P, Hainzl O et al. Stil is a noncompetitive inhibitor of the Hsp90 ATPase: Binding prevents the N-terminal dimerization reaction during the ATPase cycle. J Biol Chem 2003; 278:10328–10333.

    Article  CAS  PubMed  Google Scholar 

  58. Prodromou C, Siligardi G, O’Brien R et al. Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones. EMBO J 1999; 18:754–762.

    Article  CAS  PubMed  Google Scholar 

  59. Agarraberes FA, Dice JF. A molecular chaperone complex at the lysosomal membrane is required for protein translocation. J Cell Sci 2001; 114:2491–2499.

    CAS  PubMed  Google Scholar 

  60. Glover JR, Lindquist S. Hsp 104, Hsp70, and Hsp40: A novel chaperone system that rescues previously aggregated proteins. Cell 1998; 94:73–82.

    Article  CAS  PubMed  Google Scholar 

  61. Abbas-Terki T, Briand PA, Donzé O et al. The Hsp90 co-chaperones Cdc37 and Stil interact physically and genetically. Biol Chem 2002; 383:1335–1342.

    Article  CAS  PubMed  Google Scholar 

  62. Harst A, Lin H, Obermann WMJ. Ahal competes with Hop, p50 and p23 for binding to the molecular chaperone Hsp90 and contributes to kinase and hormone receptor activation. Biochem J 2005; 387:789–796.

    Article  CAS  PubMed  Google Scholar 

  63. Lee P, Shabbir A, Cardozo C et al. Stil and Cdc37 can stabilize Hsp90 in chaperone complexes with a protein kinase. Mol Biol Cell 2004; 15:1785–1792.

    Article  CAS  PubMed  Google Scholar 

  64. Gebauer M, Melki R, Gehring U. The chaperone cofactor Hop/p60 interacts with the cytosolic chaperonin-containing TCP-1 and affects its nucleotide exchange and protein folding activities. J Biol Chem 1998; 273:29475–29480.

    Article  CAS  PubMed  Google Scholar 

  65. Prapapanich V, Chen S, Smith DF. Mutation of Hip’s carboxy-terminal region inhibits a transitional stage of progesterone receptor assembly. Mol Cell Biol 1998; 18:944–952.

    CAS  PubMed  Google Scholar 

  66. Carrigan PE, Riggs DL, Chinkers M et al. Functional comparison of human and Drosophila Hop reveals novel role in steroid receptor maturation. J Biol Chem 2005; 280:8906–8911.

    Article  CAS  PubMed  Google Scholar 

  67. Zanata SM, Lopes MH, Mercadante AF et al. Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection. EMBO J 2002; 21:3307–3316.

    Article  CAS  PubMed  Google Scholar 

  68. Martins VR, Mercadante AF, Cabral ALB et al. Insights into the physiological function of cellular prion protein. Braz J Med Biol Res 2001; 34:585–595.

    CAS  PubMed  Google Scholar 

  69. Zheng L, Roeder RG, Luo Y. S phase activation of the histone H2B promoter by OCA-S, a coactivator complex that contains GAPDH as a key component. Cell 2003; 114:255–266.

    Article  CAS  PubMed  Google Scholar 

  70. Longshaw VM, Chappie JP, Balda MS et al. Nuclear translocation of the Hsp70/Hsp90 organizing protein mSTIl is regulated by cell cycle kinases. J Cell Sci 2004; 117:701–710.

    Article  CAS  PubMed  Google Scholar 

  71. Longshaw VM, Dirr HW, Blatch GL et al. The in vitro phosphorylation of the co-chaperone mSTIl by cell cycle kinases substantiates a predicted casein kinase II-p34cdc2-NLS (CcN) motif. Biol Chem 2000; 381:1133–1138.

    Article  CAS  PubMed  Google Scholar 

  72. Odunuga OO, Longshaw VM, Blatch GL. Hop: More than an Hsp70/Hsp90 adaptor protein. BioEssays 2004; 26:1058–1068.

    Article  CAS  PubMed  Google Scholar 

  73. Kretzschmar HA, Tings T, Madlung A et al. Function of Prp(C) as a copper-binding protein at the synapse. Arch Virol Suppl 2000; 16:239–249.

    PubMed  Google Scholar 

  74. Martins VR, Graner E, Garcia-Abreu J et al. Complementary hydropathy identifies a cellular prion protein receptor. Nat Med 1997; 3:1376–1382.

    Article  CAS  PubMed  Google Scholar 

  75. Muesch A, Hartmann E, Rohde K et al. A novel pathway for secretory proteins? Trends Biochem Sci 1990; 15:86–88.

    Article  CAS  PubMed  Google Scholar 

  76. Nollen EAA, Salomons FA, Brunsting JF et al. Dynamic changes in the localization of thermally unfolded nuclear proteins associated with chaperone-dependent protection. Proc Natl Acad Sci USA 2001; 98:12038–12043.

    Article  CAS  PubMed  Google Scholar 

  77. Diehl JA, Yang W, Rimerman RA et al. Hsc70 regulates accumulation of cyclin Dl and cyclin Dl-dependent protein kinase. Mol Cell Biol 2003; 23:1764–1774.

    Article  CAS  PubMed  Google Scholar 

  78. Biggiogera M, Tanguay RM, Marin R et al. Localization of heat shock proteins in mouse male germ cells: An immunoelectron microscopical study. Exp Cell Res 1996; 229:77–85.

    Article  CAS  PubMed  Google Scholar 

  79. Langer T, Rosmus S, Fasold H. Intracellular localization of the 90 kDa heat shock protein (HSP90d) determined by expression of a EGFP-HSP90a-fusion protein in unstressed and heat stressed 3T3 cells. Cell Biol Int 2003; 27:47–52.

    Article  CAS  PubMed  Google Scholar 

  80. Scheufler C, Brinker A, Bourenkov G et al. Structure of TPR domain-peptide complexes: Critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell 2000; 101:199–210.

    Article  CAS  PubMed  Google Scholar 

  81. DeLano WL. The PyMOL molecular graphics system. South San Francisco, CA, USA: DeLano Scientific LLC, 2005, (http://www.pymol.org.).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, Grahamstown, 6140, South Africa

    Sheril Daniel, Csaba Söti, Graeme Bradley & Gregory L. Blatch

  2. Department of Medical Chemistry, Semmelweis University, Budapest, Hungary

    Peter Csermely

Authors
  1. Sheril Daniel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Csaba Söti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Csermely
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Graeme Bradley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gregory L. Blatch
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Daniel, S., Söti, C., Csermely, P., Bradley, G., Blatch, G.L. (2007). Hop: An Hsp70/Hsp90 Co-Chaperone That Functions Within and Beyond Hsp70/Hsp90 Protein Folding Pathways. In: Networking of Chaperones by Co-Chaperones. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-49310-7_3

Download citation

Publish with us

Policies and ethics

Search

Navigation