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Annual Review of Biochemistry

Volume 85, 2016

Experimental Milestones in the Discovery of Molecular Chaperones as Polypeptide Unfolding Enzymes

Abstract

Molecular chaperones control the cellular folding, assembly, unfolding, disassembly, translocation, activation, inactivation, disaggregation, and degradation of proteins. In 1989, groundbreaking experiments demonstrated that a purified chaperone can bind and prevent the aggregation of artificially unfolded polypeptides and use ATP to dissociate and convert them into native proteins. A decade later, other chaperones were shown to use ATP hydrolysis to unfold and solubilize stable protein aggregates, leading to their native refolding. Presently, the main conserved chaperone families Hsp70, Hsp104, Hsp90, Hsp60, and small heat-shock proteins (sHsps) apparently act as unfolding nanomachines capable of converting functional alternatively folded or toxic misfolded polypeptides into harmless protease-degradable or biologically active native proteins. Being unfoldases, the chaperones can proofread three-dimensional protein structures and thus control protein quality in the cell. Understanding the mechanisms of the cellular unfoldases is central to the design of new therapies against aging, degenerative protein conformational diseases, and specific cancers.

Keyword(s): heat-shock proteins, Hsp104, Hsp110, Hsp60, Hsp70, protein homeostasis, sHsps, small heat-shock proteins, unfoldases
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2016-06-02
2024-05-20
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Literature Cited

  1. Rothman JE, Kornberg RD. 1.  1986. Cell biology: an unfolding story of protein translocation. Nature 322:209–10Suggested that cellular unfolding enzymes exist to assist protein translocation and folding and prevent aggregation. [Google Scholar]
  2. Ellis J. 2.  1987. Proteins as molecular chaperones. Nature 328:378–79 [Google Scholar]
  3. Finka A, Goloubinoff P. 3.  2013. Proteomic data from human cell cultures refine mechanisms of chaperone-mediated protein homeostasis. Cell Stress Chaperones 18:591–605 [Google Scholar]
  4. Finka A, Sood V, Quadroni M, De Los Rios P, Goloubinoff P. 4.  2015. Quantitative proteomics of heat-treated human cells show an across-the-board mild depletion of housekeeping proteins to massively accumulate few Hsps. Cell Stress Chaperones 20:605–20 [Google Scholar]
  5. Crick F. 5.  1970. Central dogma of molecular biology. Nature 227:561–63 [Google Scholar]
  6. Cressey D. 6.  2015. DNA-repair sleuths win chemistry Nobel. Nature 526:307 [Google Scholar]
  7. Hershko A, Ciechanover A, Heller H, Haas AL, Rose IA. 7.  1980. Proposed role of ATP in protein breakdown: conjugation of protein with multiple chains of the polypeptide of ATP-dependent proteolysis. PNAS 77:1783–86 [Google Scholar]
  8. Bukau B, Weissman J, Horwich A. 8.  2006. Molecular chaperones and protein quality control. Cell 125:443–51 [Google Scholar]
  9. Hinault MP, Ben-Zvi A, Goloubinoff P. 9.  2006. Chaperones and proteases: cellular fold-controlling factors of proteins in neurodegenerative diseases and aging. J. Mol. Neurosci. 30:249–65 [Google Scholar]
  10. Anfinsen CB, Sela M, Cooke JP. 10.  1962. Reversible reduction of disulfide bonds in polyalanyl ribonuclease. J. Biol. Chem. 237:1825–31 [Google Scholar]
  11. Epstein CJ, Goldberger RF, Anfinsen CB. 11.  1963. Genetic control of tertiary protein structure—studies with model systems. Cold Spring Harb. Symp. 28:439–49 [Google Scholar]
  12. Milo R. 12.  2013. What is the total number of protein molecules per cell volume? A call to rethink some published values. BioEssays 35:1050–55 [Google Scholar]
  13. Hartl FU, Martin J, Neupert W. 13.  1992. Protein folding in the cell: the role of molecular chaperones Hsp70 and Hsp60. Annu. Rev. Biophys. Biomol. Struct. 21:293–322 [Google Scholar]
  14. Ellis RJ. 14.  2001. Macromolecular crowding: obvious but underappreciated. Trends Biochem. Sci. 26:597–604 [Google Scholar]
  15. Sternberg N. 15.  1973. Properties of a mutant of Escherichia coli defective in bacteriophage λ head formation (groE): II. The propagation of phage λ. J. Mol. Biol. 76:25–44 [Google Scholar]
  16. Yochem J, Uchida H, Sunshine M, Saito H, Georgopoulos CP, Feiss M. 16.  1978. Genetic analysis of two genes, dnaJ and dnaK, necessary for Escherichia coli and bacteriophage lambda DNA replication. Mol. Gen. Genet. 164:9–14 [Google Scholar]
  17. Tilly K, Murialdo H, Georgopoulos C. 17.  1981. Identification of a second Escherichia coli groE gene whose product is necessary for bacteriophage morphogenesis. PNAS 78:1629–33 [Google Scholar]
  18. Hohn T, Hohn B, Engel A, Wurtz M, Smith PR. 18.  1979. Isolation and characterization of the host protein groE involved in bacteriophage lambda assembly. J. Mol. Biol. 129:359–73 [Google Scholar]
  19. Barraclough R, Ellis RJ. 19.  1980. Protein synthesis in chloroplasts. IX. Assembly of newly synthesized large subunits into ribulose bisphosphate carboxylase in isolated intact pea chloroplasts. Biochim. Biophys. Acta 608:19–31Provided evidence that a nascent polypeptide may associate with another protein before assembly into a mature oligomer. [Google Scholar]
  20. Laskey RA, Honda BM, Mills AD, Finch JT. 20.  1978. Nucleosomes are assembled by an acidic protein which binds histones and transfers them to DNA. Nature 275:416–20 [Google Scholar]
  21. Hemmingsen SM, Ellis RJ. 21.  1986. Purification and properties of ribulosebisphosphate carboxylase large subunit binding protein. Plant Physiol. 80:269–76 [Google Scholar]
  22. LeBowitz JH, Zylicz M, Georgopoulos C, McMacken R. 22.  1985. Initiation of DNA replication on single-stranded DNA templates catalyzed by purified replication proteins of bacteriophage λ and Escherichia coli. PNAS 82:3988–92 [Google Scholar]
  23. 23.  Deleted in proof
  24. Zylicz M, Georgopoulos C. 24.  1984. Purification and properties of the Escherichia coli DnaK replication protein. J. Biol. Chem. 259:8820–25 [Google Scholar]
  25. Osipiuk J, Georgopoulos C, Zylicz M. 25.  1993. Initiation of lambda DNA replication. The Escherichia coli small heat shock proteins, DnaJ and GrpE, increase DnaK's affinity for the lambda P protein. J. Biol. Chem. 268:4821–27 [Google Scholar]
  26. Georgopoulos CP. 26.  1977. New bacterial gene (groPC) which affects λ DNA replication. Mol. Gen. Genet. 151:35–39 [Google Scholar]
  27. Goloubinoff P, Christeller JT, Gatenby AA, Lorimer GH. 27.  1989. Reconstitution of active dimeric ribulose bisphosphate carboxylase from an unfolded state depends on two chaperonin proteins and Mg-ATP. Nature 342:884–89Provided experimental evidence that a chaperone can prevent aggregation and use ATP to mediate native protein refolding. [Google Scholar]
  28. Tissières A, Mitchell HK, Tracy UM. 28.  1974. Protein synthesis in salivary glands of Drosophila melanogaster: relation to chromosome puffs. J. Mol. Biol. 84:389–98 [Google Scholar]
  29. Finley D, Ciechanover A, Varshavsky A. 29.  1984. Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85. Cell 37:43–55 [Google Scholar]
  30. Pelham HRB. 30.  1986. Speculations on the functions of the major heat-shock and glucose-regulated proteins. Cell 46:959–61 [Google Scholar]
  31. Lewis MJ, Pelham HRB. 31.  1985. Involvement of ATP in the nuclear and nucleolar functions of the 70 kd heat-shock protein. EMBO J. 4:3137–43 [Google Scholar]
  32. Eilers M, Schatz G. 32.  1986. Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria. Nature 322:228–32 [Google Scholar]
  33. Waxman L, Goldberg AL. 33.  1985. Protease La, the lon gene product, cleaves specific fluorogenic peptides in an ATP-dependent reaction. J. Biol. Chem. 260:12022–28 [Google Scholar]
  34. Musgrove JE, Johnson RA, Ellis RJ. 34.  1987. Dissociation of the ribulosebisphosphate-carboxylase large-subunit binding protein into dissimilar subunits. Eur. J. Biochem. 163:529–34 [Google Scholar]
  35. Musgrove JE, Ellis RJ. 35.  1986. The Rubisco large subunit binding protein. Philos. Trans. B 313:419–28 [Google Scholar]
  36. Picard D, Salser SJ, Yamamoto KR. 36.  1988. A movable and regulable inactivation function within the steroid binding domain of the glucocorticoid receptor. Cell 54:1073–80 [Google Scholar]
  37. Lindquist S, Craig EA. 37.  1988. The heat-shock proteins. Annu. Rev. Genet. 22:631–77 [Google Scholar]
  38. Bochkareva ES, Lissin NM, Girshovich AS. 38.  1988. Transient association of newly synthesized unfolded proteins with the heat-shock GroEL protein. Nature 336:254–57 [Google Scholar]
  39. Deuerling E, Schulze-Specking A, Tomoyasu T, Mogk A, Bukau B. 39.  1999. Trigger factor and DnaK cooperate in folding of newly synthesized proteins. Nature 400:693–96 [Google Scholar]
  40. Pushkin AV, Tsuprun VL, Solovjeva NA, Shubin VV, Evstigneeva ZG, Kretovich WL. 40.  1982. High molecular weight pea leaf protein similar to the GroE protein of Escherichia coli. Biochim. Biophys. Acta 704:379–84 [Google Scholar]
  41. Hemmingsen SM, Woolford C, Vandervies SM, Tilly K, Dennis DT. 41.  et al. 1988. Homologous plant and bacterial proteins chaperone oligomeric protein assembly. Nature 333:330–34Reported sequence homology evidence that a chaperone can mediate the assembly of protein oligomers. [Google Scholar]
  42. Goloubinoff P, Gatenby AA, Lorimer GH. 42.  1989. GroE heat-shock proteins promote assembly of foreign prokaryotic ribulose bisphosphate carboxylase oligomers in Escherichia coli. Nature 337:44–47Provided evidence that a chaperone mediates proper folding and assembly of a foreign protein in cells. [Google Scholar]
  43. Cheng MY, Hartl FU, Horwich AL. 43.  1990. The mitochondrial chaperonin Hsp60 is required for its own assembly. Nature 348:455–58 [Google Scholar]
  44. Cheng MY, Hartl FU, Martin J, Pollock RA, Kalousek F. 44.  et al. 1989. Mitochondrial heat-shock protein Hsp60 is essential for assembly of proteins imported into yeast mitochondria. Nature 337:620–25 [Google Scholar]
  45. Milos P, Roy H. 45.  1984. ATP-released large subunits participate in the assembly of RuBP carboxylase. J. Cell Biochem. 24:153–62 [Google Scholar]
  46. Ostermann J, Horwich AL, Neupert W, Hartl FU. 46.  1989. Protein folding in mitochondria requires complex formation with Hsp60 and ATP hydrolysis. Nature 341:125–30 [Google Scholar]
  47. Hemmingsen SM, Ellis RJ. 47.  1986. Purification and properties of ribulosebisphosphate carboxylase large subunit binding protein. Plant Physiol. 80:269–76 [Google Scholar]
  48. Viitanen PV, Lubben TH, Reed J, Goloubinoff P, O'Keefe DP, Lorimer GH. 48.  1990. Chaperonin-facilitated refolding of ribulosebisphosphate carboxylase and ATP hydrolysis by chaperonin-60 (groEL) are K+ dependent. Biochemistry 29:5665–71 [Google Scholar]
  49. Horwich AL, Apetri AC, Fenton WA. 49.  2009. The GroEL/GroES cis cavity as a passive anti-aggregation device. FEBS Lett. 583:2654–62 [Google Scholar]
  50. Priya S, Sharma SK, Sood V, Mattoo RUH, Finka A. 50.  et al. 2013. GroEL and CCT are catalytic unfoldases mediating out-of-cage polypeptide refolding without ATP. PNAS 110:7199–204Reported that GroEL and CCT have intrinsic unfoldase activities but require ATP to evict oversticky intermediates. [Google Scholar]
  51. Clare DK, Vasishtan D, Stagg S, Quispe J, Farr GW. 51.  et al. 2012. ATP-triggered conformational changes delineate substrate-binding and -folding mechanics of the GroEL chaperonin. Cell 149:113–23 [Google Scholar]
  52. Goloubinoff P, Diamant S, Weiss C, Azem A. 52.  1997. GroES binding regulates GroEL chaperonin activity under heat shock. FEBS Lett. 407:215–19 [Google Scholar]
  53. Ellis RJ. 53.  1994. Molecular chaperones. Opening and closing the Anfinsen cage. Curr. Biol. 4:633–35 [Google Scholar]
  54. Martin J, Langer T, Boteva R, Schramel A, Horwich AL, Hartl FU. 54.  1991. Chaperonin-mediated protein folding at the surface of groEL through a ‘molten globule’-like intermediate. Nature 352:36–42 [Google Scholar]
  55. Buchner J, Schmidt M, Fuchs M, Jaenicke R, Rudolph R. 55.  et al. 1991. GroE facilitates refolding of citrate synthase by suppressing aggregation. Biochemistry 30:1586–91 [Google Scholar]
  56. Hartmann CM, Gehring H, Christen P. 56.  1993. The mature form of imported mitochondrial proteins undergoes conformational changes upon binding to isolated mitochondria. Eur. J. Biochem. 218:905–10 [Google Scholar]
  57. Chaudhuri TK, Farr GW, Fenton WA, Rospert S, Horwich AL. 57.  2001. GroEL/GroES-mediated folding of a protein too large to be encapsulated. Cell 107:235–46Provided experimental evidence that encapsulation is not obligate to chaperonin mechanism. [Google Scholar]
  58. Skowyra D, Georgopoulos C, Zylicz M. 58.  1990. The E. coli dnaK gene product, the hsp70 homolog, can reactivate heat-inactivated RNA polymerase in an ATP hydrolysis-dependent manner. Cell 62:939–44Reported that Hsp70s are molecular chaperones that use ATP to convert inactive polypeptides into native proteins. [Google Scholar]
  59. Langer T, Pfeifer G, Martin J, Baumeister W, Hartl FU. 59.  1992. Chaperonin-mediated protein folding: GroES binds to one end of the GroEL cylinder, which accommodates the protein substrate within its central cavity. EMBO J. 11:4757–65 [Google Scholar]
  60. Skowyra D, Wickner S. 60.  1993. The interplay of the GrpE heat shock protein and Mg2+ in RepA monomerization by DnaJ and DnaK. J. Biol. Chem. 268:25296–301 [Google Scholar]
  61. Natalello A, Mattoo RUH, Priya S, Sharma SK, Goloubinoff P, Doglia SM. 61.  2013. Biophysical characterization of two different stable misfolded monomeric polypeptides that are chaperone-amenable substrates. J. Mol. Biol. 425:1158–71 [Google Scholar]
  62. Priya S, Sharma SK, Goloubinoff P. 62.  2013. Molecular chaperones as enzymes that catalytically unfold misfolded polypeptides. FEBS Lett. 587:1981–87 [Google Scholar]
  63. Glover JR, Lindquist S. 63.  1998. Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94:73–82Provided experimental evidence that a chaperone can disaggregate and refold stable preformed protein aggregates. [Google Scholar]
  64. Slepenkov SV, Witt SN. 64.  2002. The unfolding story of the Escherichia coli Hsp70 DnaK: Is DnaK a holdase or an unfoldase?. Mol. Microbiol. 45:1197–206 [Google Scholar]
  65. Mattoo RH, Goloubinoff P. 65.  2014. Molecular chaperones are nanomachines that catalytically unfold misfolded and alternatively folded proteins. Cell. Mol. Life Sci. 71:3311–25 [Google Scholar]
  66. Netzer WJ, Hartl FU. 66.  1998. Protein folding in the cytosol: chaperonin-dependent and -independent mechanisms. Trends Biochem. Sci. 23:68–73 [Google Scholar]
  67. Kampinga HH, Garrido C. 67.  2012. HSPBs: small proteins with big implications in human disease. Int. J. Biochem. Cell Biol. 44:1706–10 [Google Scholar]
  68. Shtilerman M, Lorimer GH, Englander SW. 68.  1999. Chaperonin function: folding by forced unfolding. Science 284:822–25 [Google Scholar]
  69. Lin Z, Madan D, Rye HS. 69.  2008. GroEL stimulates protein folding through forced unfolding. Nat. Struct. Mol. Biol. 15:303–11Showed by Förster resonance energy transfer spectroscopy that GroEL has an intrinsic unfoldase activity. [Google Scholar]
  70. Libich DS, Tugarinov V, Clore GM. 70.  2015. Intrinsic unfoldase/foldase activity of the chaperonin GroEL directly demonstrated using multinuclear relaxation-based NMR. PNAS 112:8817–23Showed by nuclear magnetic resonance spectroscopy that GroEL has an intrinsic unfoldase activity. [Google Scholar]
  71. Schroder H, Langer T, Hartl FU, Bukau B. 71.  1993. Dnak, Dnaj and Grpe form a cellular chaperone machinery capable of repairing heat-induced protein damage. EMBO J. 12:4137–44 [Google Scholar]
  72. Rudiger S, Germeroth L, Schneider-Mergener J, Bukau B. 72.  1997. Substrate specificity of the DnaK chaperone determined by screening cellulose-bound peptide libraries. EMBO J. 16:1501–7 [Google Scholar]
  73. Sharma SK, De Los Rios P, Christen P, Lustig A, Goloubinoff P. 73.  2010. The kinetic parameters and energy cost of the Hsp70 chaperone as a polypeptide unfoldase. Nat. Chem. Biol. 6:914–20Reported that Hsp70 uses ATP to catalytically unfold stable misfolded proteins; their subsequent native refolding is spontaneous. [Google Scholar]
  74. Mattoo RUH, Sharma SK, Priya S, Finka A, Goloubinoff P. 74.  2013. Hsp110 is a bona fide chaperone using ATP to unfold stable misfolded polypeptides and reciprocally collaborate with Hsp70 to solubilize protein aggregates. J. Biol. Chem. 288:21399–411 [Google Scholar]
  75. Clerico EM, Tilitsky JM, Meng W, Gierasch LM. 75.  2015. How Hsp70 molecular machines interact with their substrates to mediate diverse physiological functions. J. Mol. Biol. 427:1575–88 [Google Scholar]
  76. De Los Rios P, Ben-Zvi A, Slutsky O, Azem A, Goloubinoff P. 76.  2006. Hsp70 chaperones accelerate protein translocation and the unfolding of stable protein aggregates by entropic pulling. PNAS 103:6166–71Provided evidence that Hsp70 chaperones can unfold misfolded polypeptide substrates by cooperative entropic pulling. [Google Scholar]
  77. Vembar SS, Jonikas MC, Hendershot LM, Weissman JS, Brodsky JL. 77.  2010. J domain co-chaperone specificity defines the role of BiP during protein translocation. J. Biol. Chem. 285:22484–94 [Google Scholar]
  78. Griesemer M, Young C, Robinson AS, Petzold L. 78.  2014. BiP clustering facilitates protein folding in the endoplasmic reticulum. PLOS Comput. Biol. 10:e1003675 [Google Scholar]
  79. Tiwari S, Kumar V, Jayaraj GG, Maiti S, Mapa K. 79.  2013. Unique structural modulation of a non-native substrate by cochaperone DnaJ. Biochemistry 52:1011–18 [Google Scholar]
  80. Kellner R, Hofmann H, Barducci A, Wunderlich B, Nettels D, Schuler B. 80.  2014. Single-molecule spectroscopy reveals chaperone-mediated expansion of substrate protein. PNAS 111:13355–60 [Google Scholar]
  81. Goldstein LE, Muffat JA, Cherny RA, Moir RD, Ericsson MH. 81.  et al. 2003. Cytosolic β-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease. Lancet 361:1258–65 [Google Scholar]
  82. Muchowski PJ, Clark JI. 82.  1998. ATP-enhanced molecular chaperone functions of the small heat shock protein human αB crystallin. PNAS 95:1004–9 [Google Scholar]
  83. Biswas A, Das KP. 83.  2004. Role of ATP on the interaction of α-crystallin with its substrates and its implications for the molecular chaperone function. J. Biol. Chem. 279:42648–57 [Google Scholar]
  84. Ghosh JG, Houck SA, Doneanu CE, Clark JI. 84.  2006. The β4-β8 groove is an ATP-interactive site in the α crystallin core domain of the small heat shock protein, human αB crystallin. J. Mol. Biol. 364:364–75 [Google Scholar]
  85. Giese KC, Vierling E. 85.  2002. Changes in oligomerization are essential for the chaperone activity of a small heat shock protein in vivo and in vitro. J. Biol. Chem. 277:46310–18 [Google Scholar]
  86. Stengel F, Baldwin AJ, Painter AJ, Jaya N, Basha E. 86.  et al. 2010. Quaternary dynamics and plasticity underlie small heat shock protein chaperone function. PNAS 107:2007–12 [Google Scholar]
  87. Veinger L, Diamant S, Buchner J, Goloubinoff P. 87.  1998. The small heat-shock protein IbpB from Escherichia coli stabilizes stress-denatured proteins for subsequent refolding by a multichaperone network. J. Biol. Chem. 273:11032–37 [Google Scholar]
  88. Lee GJ, Roseman AM, Saibil HR, Vierling E. 88.  1997. A small heat shock protein stably binds heat-denatured model substrates and can maintain a substrate in a folding-competent state. EMBO J. 16:659–71 [Google Scholar]
  89. Todd MJ, Lorimer GH, Thirumalai D. 89.  1996. Chaperonin-facilitated protein folding: optimization of rate and yield by an iterative annealing mechanism. PNAS 93:4030–35Showed that GroEL chaperonins act upon their substrate by causing local unfolding with an iterative annealing mechanism. [Google Scholar]
  90. Wiech H, Buchner J, Zimmermann R, Jakob U. 90.  1992. Hsp90 chaperones protein folding in vitro. Nature 358:169–70 [Google Scholar]
  91. Rohl A, Rohrberg J, Buchner J. 91.  2013. The chaperone Hsp90: changing partners for demanding clients. Trends Biochem. Sci. 38:253–62 [Google Scholar]
  92. Hartl FU, Bracher A, Hayer-Hartl M. 92.  2011. Molecular chaperones in protein folding and proteostasis. Nature 475:324–32 [Google Scholar]
  93. Walerych D, Gutkowska M, Klejman MP, Wawrzynow B, Tracz Z. 93.  et al. 2010. ATP binding to Hsp90 is sufficient for effective chaperoning of p53 protein. J. Biol. Chem. 285:32020–28 [Google Scholar]
  94. Ziemienowicz A, Zylicz M, Floth C, Hubscher U. 94.  1995. Calf thymus Hsc70 protein protects and reactivates prokaryotic and eukaryotic enzymes. J. Biol. Chem. 270:15479–84 [Google Scholar]
  95. Diamant S, Ben-Zvi AP, Bukau B, Goloubinoff P. 95.  2000. Size-dependent disaggregation of stable protein aggregates by the DnaK chaperone machinery. J. Biol. Chem. 275:21107–13 [Google Scholar]
  96. Zolkiewski M. 96.  1999. ClpB cooperates with DnaK, DnaJ, and GrpE in suppressing protein aggregation. A novel multi-chaperone system from Escherichia coli. J. Biol. Chem. 274:28083–86 [Google Scholar]
  97. Goloubinoff P, Mogk A, Ben Zvi AP, Tomoyasu T, Bukau B. 97.  1999. Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network. PNAS 96:13732–37 [Google Scholar]
  98. Sauer RT, Baker TA. 98.  2011. AAA+ proteases: ATP-fueled machines of protein destruction. Annu. Rev. Biochem. 80:587–612 [Google Scholar]
  99. Carroni M, Kummer E, Oguchi Y, Wendler P, Clare DK. 99.  et al. 2014. Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation. eLife 3:e02481 [Google Scholar]
  100. Seyffer F, Kummer E, Oguchi Y, Winkler J, Kumar M. 100.  et al. 2012. Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA plus disaggregase at aggregate surfaces. Nat. Struct. Mol. Biol. 19:1347–55 [Google Scholar]
  101. Aubin-Tam ME, Olivares AO, Sauer RT, Baker TA, Lang MJ. 101.  2011. Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine. Cell 145:257–67 [Google Scholar]
  102. Zolkiewski M. 102.  2006. A camel passes through the eye of a needle: protein unfolding activity of Clp ATPases. Mol. Microbiol. 61:1094–100 [Google Scholar]
  103. Weibezahn J, Tessarz P, Schlieker C, Zahn R, Maglica Z. 103.  et al. 2004. Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB. Cell 119:653–65 [Google Scholar]
  104. Iosefson O, Nager AR, Baker TA, Sauer RT. 104.  2015. Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine. Nat. Chem. Biol. 11:201–6 [Google Scholar]
  105. Shorter J. 105.  2011. The mammalian disaggregase machinery: Hsp110 synergizes with Hsp70 and Hsp40 to catalyze protein disaggregation and reactivation in a cell-free system. PLOS ONE 6:e26319 [Google Scholar]
  106. Rampelt H, Kirstein-Miles J, Nillegoda NB, Chi K, Scholz SR. 106.  et al. 2012. Metazoan Hsp70 machines use Hsp110 to power protein disaggregation. EMBO J. 31:4221–35 [Google Scholar]
  107. Schuermann JP, Jiang J, Cuellar J, Llorca O, Wang L. 107.  et al. 2008. Structure of the Hsp110:Hsc70 nucleotide exchange machine. Mol. Cell 31:232–43 [Google Scholar]
  108. Torrente MP, Shorter J. 108.  2014. The metazoan protein disaggregase and amyloid depolymerase system: Hsp110, Hsp70, Hsp40, and small heat shock proteins. Prion 7:457–63 [Google Scholar]
  109. Ebrahimi-Fakhari D, Wahlster L, McLean PJ. 109.  2012. Protein degradation pathways in Parkinson's disease: curse or blessing. Acta Neuropathol. 124:153–72 [Google Scholar]
  110. Zempel H, Mandelkow E. 110.  2014. Lost after translation: missorting of Tau protein and consequences for Alzheimer disease. Trends Neurosci. 37:721–32 [Google Scholar]
  111. Farr GW, Fenton WA, Chaudhuri TK, Clare DK, Saibil HR, Horwich AL. 111.  2003. Folding with and without encapsulation by cis- and trans-only GroEL-GroES complexes. EMBO J. 22:3220–30 [Google Scholar]
  112. Weiss C, Goloubinoff P. 112.  1995. A mutant at position 87 of the GroEL chaperonin is affected in protein binding and ATP hydrolysis. J. Biol. Chem. 270:13956–60 [Google Scholar]
  113. Azia A, Unger R, Horovitz A. 113.  2012. What distinguishes GroEL substrates from other Escherichia coli proteins?. FEBS J. 279:543–50 [Google Scholar]
  114. Rudiger S, Schneider-Mergener J, Bukau B. 114.  2001. Its substrate specificity characterizes the DnaJ co-chaperone as a scanning factor for the DnaK chaperone. EMBO J. 20:1042–50 [Google Scholar]
  115. Stan G, Thirumalai D, Lorimer GH, Brooks BR. 115.  2003. Annealing function of GroEL: structural and bioinformatic analysis. Biophys. Chem. 100:453–67 [Google Scholar]
  116. Tokuriki N, Tawfik DS. 116.  2009. Chaperonin overexpression promotes genetic variation and enzyme evolution. Nature 459:668–73 [Google Scholar]
  117. Bandyopadhyay A, Saxena K, Kasturia N, Dalal V, Bhatt N. 117.  et al. 2012. Chemical chaperones assist intracellular folding to buffer mutational variations. Nat. Chem. Biol. 8:238–45 [Google Scholar]
  118. Jarosz DF, Lindquist S. 118.  2010. Hsp90 and environmental stress transform the adaptive value of natural genetic variation. Science 330:1820–24 [Google Scholar]
  119. de Los Rios P, Goloubinoff P. 119.  2012. Protein folding chaperoning protein evolution. Nat. Chem. Biol. 8:226–28 [Google Scholar]
  120. Finka A, Mattoo RUH, Goloubinoff P. 120.  2011. Meta-analysis of heat- and chemically upregulated chaperone genes in plant and human cells. Cell Stress Chaperones 16:15–31 [Google Scholar]
  121. Wolff S, Weissman JS, Dillin A. 121.  2014. Differential scales of protein quality control. Cell 157:52–64 [Google Scholar]
  122. Hinault MP, Goloubinoff P. 122.  2007. Molecular crime and cellular punishment: active detoxification of misfolded and aggregated proteins in the cell by the chaperone and protease networks. Adv. Exp. Med. Biol. 594:47–54 [Google Scholar]
  123. Brehme M, Voisine C, Rolland T, Wachi S, Soper JH. 123.  et al. 2014. A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. Cell Rep. 9:1135–50 [Google Scholar]
  124. Labbadia J, Morimoto RI. 124.  2015. The biology of proteostasis in aging and disease. Annu. Rev. Biochem. 84:435–64 [Google Scholar]
  125. Johnson KA. 125.  2010. The kinetic and chemical mechanism of high-fidelity DNA polymerases. Biochim. Biophys. Acta 1804:1041–48 [Google Scholar]
  126. Fasken MB, Corbett AH. 126.  2005. Process or perish: quality control in mRNA biogenesis. Nat. Struct. Mol. Biol. 12:482–88 [Google Scholar]
  127. Yadavalli SS, Ibba M. 127.  2012. Quality control in aminoacyl-tRNA synthesis: its role in translational fidelity. Adv. Protein Chem. Struct. Biol. 86:1–43 [Google Scholar]
  128. Hinault MP, Cuendet AFH, Mattoo RUH, Mensi M, Dietler G. 128.  et al. 2010. Stable α-synuclein oligomers strongly inhibit chaperone activity of the Hsp70 system by weak interactions with J-domain co-chaperones. J. Biol. Chem. 285:38173–82 [Google Scholar]
  129. Doyle SM, Genest O, Wickner S. 129.  2013. Protein rescue from aggregates by powerful molecular chaperone machines. Nat. Rev. Mol. Cell. Biol. 14:617–29 [Google Scholar]
  130. Bromberg Z, Goloubinoff P, Saidi Y, Weiss YG. 130.  2013. The membrane-associated transient receptor potential vanilloid channel is the central heat shock receptor controlling the cellular heat shock response in epithelial cells. PLOS ONE 8:e57149 [Google Scholar]
  131. Finka A, Cuendet AFH, Maathuis FJM, Saidi Y, Goloubinoff P. 131.  2012. Plasma membrane cyclic nucleotide gated calcium channels control land plant thermal sensing and acquired thermotolerance. Plant Cell 24:3333–48 [Google Scholar]
  132. Whitesell L, Santagata S, Lin NU. 132.  2012. Inhibiting Hsp90 to treat cancer: a strategy in evolution. Curr. Mol. Med. 12:1108–24 [Google Scholar]
  133. McConnell JR, McAlpine SR. 133.  2013. Heat shock proteins 27, 40, and 70 as combinational and dual therapeutic cancer targets. Bioorg. Med. Chem. Lett. 23:1923–28 [Google Scholar]
  134. Saidi Y, Finka A, Muriset M, Bromberg Z, Weiss YG. 134.  et al. 2009. The heat shock response in moss plants is regulated by specific calcium-permeable channels in the plasma membrane. Plant Cell 21:2829–43 [Google Scholar]
  135. Mittler R, Finka A, Goloubinoff P. 135.  2012. How do plants feel the heat?. Trends Biochem. Sci. 37:118–25 [Google Scholar]
  136. Saidi Y, Finka A, Goloubinoff P. 136.  2011. Heat perception and signalling in plants: a tortuous path to thermotolerance. New Phytol. 190:556–65 [Google Scholar]
  137. Kampinga HH, Hageman J, Vos MJ, Kubota H, Tanguay RM. 137.  et al. 2009. Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 14:105–11 [Google Scholar]
  138. Karagoz GE, Duarte AMS, Akoury E, Ippel H, Biernat J. 138.  et al. 2014. Hsp90-Tau complex reveals molecular basis for specificity in chaperone action. Cell 156:963–74 [Google Scholar]
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Experimental Milestones in the Discovery of Molecular Chaperones as Polypeptide Unfolding Enzymes
Annual Review of Biochemistry 85, 715 (2016); https://doi.org/10.1146/annurev-biochem-060815-014124
/content/journals/10.1146/annurev-biochem-060815-014124
/content/journals/10.1146/annurev-biochem-060815-014124
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