Advertisement

Molecular Chaperones HSP70 and HSP60 in Protein Folding and Membrane Translocation

  • Jörg Martin
  • F.-Ulrich Hartl
Conference paper
Part of the NATO ASI Series book series (volume 74)

Abstract

Given the difficulties protein chemists may encounter when attempting to renature unfolded proteins in vitro,it is noteworthy that the acquisition of the correctly folded structure seems to be much less of a traumatic experience for a nascent polypeptide chain in vivo. Generally, unfolded polypeptides have the tendency to aggregate. The cellular environment with its extremely high concentration of total protein (~0.3 g/ml) and of newly-synthesized, folding chains (30–50 μM in Escherichia coli) may result in even further reduction of solubility and thus should strongly favor misfolding and aggregation of a folding protein (Zimmerman and Trach, 1991). Nevertheless, the yield of folded protein in vivo can reach almost 100% (Gething et al., 1986). It has become clear over recent years that the action of molecular chaperones, helper proteins which interact with folding intermediates and prevent unproductive off-pathway reactions (Ellis, 1987; Rothman, 1989; Gething and Sambrook, 1992), is essential in accomplishing this high efficiency of physiological protein folding.

Keywords

Molecular Chaperone Folding Protein Folding Pathway Folding Intermediate Chaperone DnaK 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Atencio DP, Yaffe MP (1992) MASS, a yeast homolog of DnaJ involved in mitochondria! protein import. Mol Cell Biol 12: 283–291PubMedGoogle Scholar
  2. Beckman RP, Mizzen LA, Welch WJ (1990) Interaction of hsp70 with newly synthesized proteins: implications for protein folding and assembly. Science 248: 850–854CrossRefGoogle Scholar
  3. Caplan AJ, Douglas MG (1991) Characterization of YDJ1: a yeast homologue of the bacterial dnaJ protein. J Cell Biol 114: 609–621PubMedCrossRefGoogle Scholar
  4. Chandrasekhar GN, Tilly K, Woolford C, Hendrix R, Georgopoulos C (1986) Purification and properties of the groES morphogenetic protein of Escherichia coli. J Biol Chem 21: 12414–12419Google Scholar
  5. Cheng MY, Hartl FU, Martin J, Pollock RA, Kalousek F, Neupert W, Hallberg EM, Hallberg RL, Norwich AL (1989) Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported in yeast mitochondria. Nature 337: 620–625PubMedCrossRefGoogle Scholar
  6. Deshaies RJ, Koch BD, Werner-Washburne M, Craig EA, Schekman R (1988) A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332: 800–805PubMedCrossRefGoogle Scholar
  7. Ellis RJ (1987) Proteins as molecular chaperones. Nature 328: 378–379PubMedCrossRefGoogle Scholar
  8. Ellis RJ (1990) Molecular chaperones: the plant connection. Science 250:954–959 Flaherty KM, DeLuca-Flaherty, McKay DB (1990) Three-dimensional structure ofGoogle Scholar
  9. the ATPase fragment of a 70K heat-shock cognate protein. Nature 346:623–628Google Scholar
  10. Flynn GC, Pohl J, Fiocco MT, Rothman JE (1991) Peptide-binding specificity of the molecular chaperone BiP. Nature 353: 726–730PubMedCrossRefGoogle Scholar
  11. Friedman, DE, Olson ER, Georgopoulos C, Tilly K, Herskowitz I, Banuett F (1984) Interactions of bacteriophage and host macromolecules in the growth of bacteriophage X.Microbiol Rev 48: 299–325Google Scholar
  12. Gething MJ, McCammon K, Sambrook J (1986) Expression of wild type and mutant forms of influenza hemagglutinin: the role of folding in intracellular transport. Cell 46: 939–950PubMedCrossRefGoogle Scholar
  13. Gething MJ, Sambrook J (1992) Protein folding in the cell. Nature 355:33–45 Hart! FU, Neupert W (1990) Protein sorting to mitochondria: evolutionary conservations of folding and assembly. Science 247: 930–938Google Scholar
  14. Hartl FU, Martin J, Neupert W (1992) Protein folding in the cell: the role of molecular chaperones hsp70 and hsp60. Annu Rev Biophys Biomol Struct 21: 293–322PubMedCrossRefGoogle Scholar
  15. Hendrix RW (1979) Purification and properties of groE, a host protein in bacteriophage assembly. J Mol Biol 129: 375–392PubMedCrossRefGoogle Scholar
  16. Hohn T, Hohn B, Engel A, Wurtz M (1979) Isolation and characterization of the host protein groE involved in bacteriophage lambda assembly. J Mol Biol 129:359–373PubMedCrossRefGoogle Scholar
  17. Kang PJ, Ostermann J, Shilling J, Neupert W, Craig EA, Pfanner N (1990) Requirement of hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins. Nature 348: 137–143PubMedCrossRefGoogle Scholar
  18. Koll H, Guiard B, Rassow J, Ostermann J, Norwich AL, Neupert W, Hartl FU (1992) Antifolding activity of hsp60 couples protein import into the mitochondrial matrix with export to the intermembrane space. Cell 68: 1163–1175PubMedCrossRefGoogle Scholar
  19. Landry SJ, Jordan R, McMacken R, Gierasch LM (1992) Different conformations for the same polypeptide bound to chaperones DnaK and GroEL. Nature 355: 455–457PubMedCrossRefGoogle Scholar
  20. Langer T, Lu C, Echols H, Flanagan J, Hayer MK, Hartl FU (1992) Successive action of molecular chaperones DnaK, DnaJ and GroEL along the pathway of assisted protein folding. Nature 356: 683–689Google Scholar
  21. Liberek K, Marszalek J, Ang D, Georgopoulos C, Zylicz M (1991) Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proc Nati Acad Sci USA 88: 2874–2878Google Scholar
  22. Luke MM, Sutton A, Arndt KT (1991) Characterization of SIS1, a Saccharomyces cerevisiae homologue of bacterial dnaJ proteins. J Cell Biol 114: 623–638PubMedCrossRefGoogle Scholar
  23. Manning-Krieg UC, Scherer PE, Schatz G (1991) Sequential action of mitochondrial chaperones in protein import into the matrix. EMBO J 10: 3273–3280PubMedGoogle Scholar
  24. Martin J, Mahlke K, Pfanner N (1991a) Role of an energized inner membrane in mitochondria) protein import. J Biol Chem 266: 18051–18057PubMedGoogle Scholar
  25. Martin J, Langer T, Boteva R, Schramel A, Norwich AL, Hartl FU (1991 b) Chaperonin-mediated protein folding at the surface of groEL through a ‘molten globule’-like intermediate. Nature 352: 36–42Google Scholar
  26. Neupert W, Hartl FU, Craig EA, Pfanner N (1990) How do polypeptides cross the mitochondria) membranes? Cell 63: 447–450PubMedCrossRefGoogle Scholar
  27. Ostermann J, Horwich AL, Neupert W, Hartl FU (1989) Protein folding in mitochondria requires complex formation with hsp60 and ATP hydrolysis. Nature 341: 125–130PubMedCrossRefGoogle Scholar
  28. Ostermann J, Voos W, Kang PJ, Craig EA, Neupert W, Pfanner N (1990) Precursor proteins in transit through mitochondrial contact sites interact with hsp70 in the matrix. FEBS Lett 277: 281–284PubMedCrossRefGoogle Scholar
  29. Pfanner N, Hartl FU, Guiard B, Neupert W (1987) Mitochondria) precursor proteins are imported through a hydrophilic membrane environment. Eur J Biochem 169: 289–293PubMedCrossRefGoogle Scholar
  30. Phipps BM, Hoffman A, Stetter KO, Baumeister W (1991) A novel ATPase complex selectively accumulated upon heat shock is a major cellular component of thermophilic archaebacteria. EMBO J 10: 1711–1722PubMedGoogle Scholar
  31. Rassow J, Hartl FU, Guiard B, Pfanner N, Neupert W (1990) Polypeptides traverseGoogle Scholar
  32. the mitochondrial envelope in an extended state. FEBS Lett 275:190–194 Rothman JE (1989) Polypeptide chain binding proteins: catalysts of protein folding and related processes in cells. Cell 59: 591–601Google Scholar
  33. Scherer PE, Krieg UC, Hwang ST, Vestweber D, Schatz G (1990) A precursor protein partly translocated into yeast mitochondria is bound to a 70 kd mitochondrial stress protein. EMBO J 9: 4315–4322PubMedGoogle Scholar
  34. Trent JD, Nimmesgern E, Wall JS, Hartl FU, Horwich AL (1991) A molecular chaperone from a thermophilic archaebacterium is related to the eukaryotic protein t-complex polypeptide-1. Nature 354: 490–493PubMedCrossRefGoogle Scholar
  35. Viitanen PV, Donaldson GK, Lorimer GH, Lubben TH, Gatenby AA (1991) Complex interactions between chaperonin 60 molecular chaperone and dihydrofolate reductase. Biochemistry 30: 9716–9723PubMedCrossRefGoogle Scholar
  36. Wickner S, Hoskins J, McKenney K (1991 a) Function of DnaJ and DnaK as chaperones in origin-specific DNA binding by RepA. Nature 350: 165–167Google Scholar
  37. Wickner W, Driessen AJM, Hartl FU (1991b) The enzymology of protein translocation across the Escherichia coli plasma membrane. Annu Rev Biochem 60: 101–124PubMedCrossRefGoogle Scholar
  38. Zimmerman SB, Trach SO (1991) Estimation of macromolecule concentrations and excluded volume effects for the cytoplasm of Escherichia coli. J Mol Biol 222: 599–620PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • Jörg Martin
    • 1
  • F.-Ulrich Hartl
    • 1
  1. 1.Program of Cellular Biochemistry & BiophysicsSloan-Kettering InstituteNew YorkUSA

Personalised recommendations