1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Biophysics
  4. Volume 43, 2014
  5. Article

Annual Review of Biophysics

Volume 43, 2014

Mechanisms of Cellular Proteostasis: Insights from Single-Molecule Approaches

Abstract

Cells employ a variety of strategies to maintain proteome homeostasis. Beginning during protein biogenesis, the translation machinery and a number of molecular chaperones promote correct de novo folding of nascent proteins even before synthesis is complete. Another set of molecular chaperones helps to maintain proteins in their functional, native state. Polypeptides that are no longer needed or pose a threat to the cell, such as misfolded proteins and aggregates, are removed in an efficient and timely fashion by ATP-dependent proteases. In this review, we describe how applications of single-molecule manipulation methods, in particular optical tweezers, are shedding new light on the molecular mechanisms of quality control during the life cycles of proteins.

Keyword(s): chaperones, force spectroscopy, proteases, protein folding, ribosome, worm-like chain
Loading

Article metrics loading...

/content/journals/10.1146/annurev-biophys-051013-022811
2014-05-06
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/biophys/43/1/annurev-biophys-051013-022811.html?itemId=/content/journals/10.1146/annurev-biophys-051013-022811&mimeType=html&fmt=ahah

Literature Cited

  1. Abdelhakim AH, Oakes EC, Sauer RT, Baker TA. 1.  2008. Unique contacts direct high-priority recognition of the tetrameric Mu transposase-DNA complex by the AAA+ unfoldase ClpX. Mol. Cell 30:39–50 [Google Scholar]
  2. Adachi K, Oiwa K, Nishizaka T, Furuike S, Noji H. 2.  et al. 2007. Coupling of rotation and catalysis in F1-ATPase revealed by single-molecule imaging and manipulation. Cell 130:309–21 [Google Scholar]
  3. Bell GI. 3.  1978. Models for the adhesion of cells to cells. Science 200:618–27 [Google Scholar]
  4. Aitken CE, Petrov A, Puglisi JD. 4.  2010. Single ribosome dynamics and the mechanism of translation. Annu. Rev. Biophys. 39:491–513 [Google Scholar]
  5. Ashkin A. 5.  1970. Acceleration and trapping of particles by radiation pressure. Phys. Rev. Lett. 24:156–59 [Google Scholar]
  6. Ashkin A, Dziedzic JM, Bjorkholm JE, Chu S. 6.  1986. Observation of a single-beam gradient force optical trap for dielectric particles. Opt. Lett. 11:288–90 [Google Scholar]
  7. Aubin-Tam ME, Olivares AO, Sauer RT, Baker TA, Lang MJ. 7.  2011. Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine. Cell 145:257–67 [Google Scholar]
  8. Bechtluft P, van Leeuwen RG, Tyreman M, Tomkiewicz D, Nouwen N. 8.  et al. 2007. Direct observation of chaperone-induced changes in a protein folding pathway. Science 318:1458–61 [Google Scholar]
  9. Bhushan S, Gartmann M, Halic M, Armache JP, Jarasch A. 9.  et al. 2010. α-Helical nascent polypeptide chains visualized within distinct regions of the ribosomal exit tunnel. Nat. Struct. Mol. Biol. 17:313–17 [Google Scholar]
  10. Bhushan S, Hoffmann T, Seidelt B, Frauenfeld J, Mielke T. 10.  et al. 2011. SecM-stalled ribosomes adopt an altered geometry at the peptidyl transferase center. PLoS Biol. 9:e1000581 [Google Scholar]
  11. Bhushan S, Meyer H, Starosta AL, Becker T, Mielke T. 11.  et al. 2010. Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide. Mol. Cell 40:138–46 [Google Scholar]
  12. Blanchard SC, Cooperman BS, Wilson DN. 12.  2010. Probing translation with small-molecule inhibitors. Chem. Biol. 17:633–45 [Google Scholar]
  13. Borgia A, Williams PM, Clarke J. 13.  2008. Single-molecule studies of protein folding. Annu. Rev. Biochem. 77:101–25 [Google Scholar]
  14. Bustamante C. 14.  2008. In singulo biochemistry: When less is more. Annu. Rev. Biochem. 77:45–50 [Google Scholar]
  15. Bustamante C, Chemla YR, Forde NR, Izhaky D. 15.  2004. Mechanical processes in biochemistry. Annu. Rev. Biochem. 73:705–48 [Google Scholar]
  16. Bustamante C, Marko JF, Siggia ED, Smith S. 16.  1994. Entropic elasticity of lambda-phage DNA. Science 265:1599–600 [Google Scholar]
  17. Bustamante C, Macosko JC, Wuite GJ. 17.  2000. Grabbing the cat by the tail: manipulating molecules one by one. Nat. Rev. Mol. Cell Biol. 1:130–36 [Google Scholar]
  18. Camberg JL, Hoskins JR, Wickner S. 18.  2011. The interplay of ClpXP with the cell division machinery in Escherichia coli. J. Bacteriol. 193:1911–18 [Google Scholar]
  19. Cecconi C, Shank EA, Bustamante C, Marqusee S. 19.  2005. Direct observation of the three-state folding of a single protein molecule. Science 309:2057–60 [Google Scholar]
  20. Chakraborty K, Chatila M, Sinha J, Shi Q, Poschner BC. 20.  et al. 2010. Chaperonin-catalyzed rescue of kinetically trapped states in protein folding. Cell 142:112–22 [Google Scholar]
  21. Chemla YR, Aathavan K, Michaelis J, Grimes S, Jardine PJ. 21.  et al. 2005. Mechanism of force generation of a viral DNA packaging motor. Cell 122:683–92 [Google Scholar]
  22. Collin D, Ritort F, Jarzynski C, Smith SB, Tinoco I, Bustamante C. 22.  2005. Verification of the Crooks fluctuation theorem and recovery of RNA folding free energies. Nature 437:231–34 [Google Scholar]
  23. Comstock MJ, Ha T, Chemla YR. 23.  2011. Ultrahigh-resolution optical trap with single-fluorophore sensitivity. Nat. Methods 8:335–40 [Google Scholar]
  24. Crooks GE. 24.  1999. Entropy production fluctuation theorem and the nonequilibrium work relation for free energy differences. Phys. Rev. E 60:2721–26 [Google Scholar]
  25. Deniz AA, Mukhopadhyay S, Lemke EA. 25.  2008. Single-molecule biophysics: at the interface of biology, physics and chemistry. J. R. Soc. Interface 5:15–45 [Google Scholar]
  26. Dong J, Castro CE, Boyce MC, Lang MJ, Lindquist S. 26.  2010. Optical trapping with high forces reveals unexpected behaviors of prion fibrils. Nat. Struct. Mol. Biol. 17:1422–30 [Google Scholar]
  27. Dudko OK, Hummer G, Szabo A. 27.  2008. Theory, analysis, and interpretation of single-molecule force spectroscopy experiments. Proc. Natl. Acad. Sci. USA 105:15755–60 [Google Scholar]
  28. Elcock AH. 28.  2006. Molecular simulations of cotranslational protein folding: fragment stabilities, folding cooperativity, and trapping in the ribosome. PLoS Comput. Biol. 2:e98 [Google Scholar]
  29. Ellis JP, Bakke CK, Kirchdoerfer RN, Jungbauer LM, Cavagnero S. 29.  2008. Chain dynamics of nascent polypeptides emerging from the ribosome. ACS Chem. Biol. 3:555–66 [Google Scholar]
  30. Elms PJ, Chodera JD, Bustamante C, Marqusee S. 30.  2012. The molten globule state is unusually deformable under mechanical force. Proc. Natl. Acad. Sci. USA 109:3796–801 [Google Scholar]
  31. Fisher TE, Marszalek PE, Fernandez JM. 31.  2000. Stretching single molecules into novel conformations using the atomic force microscope. Nat. Struct. Biol. 7:719–24 [Google Scholar]
  32. Frank J, Gonzalez RL Jr. 32.  2010. Structure and dynamics of a processive Brownian motor: the translating ribosome. Annu. Rev. Biochem. 79:381–412 [Google Scholar]
  33. Glynn SE, Martin A, Nager AR, Baker TA, Sauer RT. 33.  2009. Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine. Cell 139:744–56 [Google Scholar]
  34. Glynn SE, Nager AR, Baker TA, Sauer RT. 34.  2012. Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine. Nat. Struct. Mol. Biol. 19:616–22 [Google Scholar]
  35. Gorbatyuk B, Marczynski GT. 35.  2005. Regulated degradation of chromosome replication proteins DnaA and CtrA in Caulobacter crescentus. Mol. Microbiol. 55:1233–45 [Google Scholar]
  36. Gottesman S, Roche E, Zhou Y, Sauer RT. 36.  1998. The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system. Genes Dev. 12:1338–47 [Google Scholar]
  37. Hartl FU, Bracher A, Hayer-Hartl M. 37.  2011. Molecular chaperones in protein folding and proteostasis. Nature 475:324–32 [Google Scholar]
  38. Hinczewski M, Gebhardt JC, Rief M, Thirumalai D. 38.  2013. From mechanical folding trajectories to intrinsic energy landscapes of biopolymers. Proc. Natl. Acad. Sci. USA 110:4500–5 [Google Scholar]
  39. Hofmann H, Hillger F, Pfeil SH, Hoffmann A, Streich D. 39.  et al. 2010. Single-molecule spectroscopy of protein folding in a chaperonin cage. Proc. Natl. Acad. Sci. USA 107:11793–98 [Google Scholar]
  40. Horwich AL, Weber-Ban EU, Finley D. 40.  1999. Chaperone rings in protein folding and degradation. Proc. Natl. Acad. Sci. USA 96:11033–40 [Google Scholar]
  41. Hoyt MA, Zich J, Takeuchi J, Zhang M, Govaerts C, Coffino P. 41.  2006. Glycine-alanine repeats impair proper substrate unfolding by the proteasome. EMBO J. 25:1720–29 [Google Scholar]
  42. Hsu ST, Cabrita LD, Fucini P, Dobson CM, Christodoulou J. 42.  2009. Structure, dynamics and folding of an immunoglobulin domain of the gelation factor (ABP-120) from Dictyostelium discoideum. J. Mol. Biol. 388:865–79 [Google Scholar]
  43. Hsu ST, Fucini P, Cabrita LD, Launay H, Dobson CM, Christodoulou J. 43.  2007. Structure and dynamics of a ribosome-bound nascent chain by NMR spectroscopy. Proc. Natl. Acad. Sci. USA 104:16516–21 [Google Scholar]
  44. Jarzynski C. 44.  1997. Nonequilibrium equality for free energy differences. Phys. Rev. Lett. 78:2690–93 [Google Scholar]
  45. Jiang Y, Douglas NR, Conley NR, Miller EJ, Frydman J, Moerner WE. 45.  2011. Sensing cooperativity in ATP hydrolysis for single multisubunit enzymes in solution. Proc. Natl. Acad. Sci. USA 108:16962–67 [Google Scholar]
  46. Kaiser CM, Chang HC, Agashe VR, Lakshmipathy SK, Etchells SA. 46.  et al. 2006. Real-time observation of trigger factor function on translating ribosomes. Nature 444:455–60 [Google Scholar]
  47. Kaiser CM, Goldman DH, Chodera JD, Tinoco I Jr, Bustamante C. 47.  2011. The ribosome modulates nascent protein folding. Science 334:1723–27 [Google Scholar]
  48. Kenniston JA, Baker TA, Fernandez JM, Sauer RT. 48.  2003. Linkage between ATP consumption and mechanical unfolding during the protein processing reactions of an AAA+ degradation machine. Cell 114:511–20 [Google Scholar]
  49. Kenniston JA, Baker TA, Sauer RT. 49.  2005. Partitioning between unfolding and release of native domains during ClpXP degradation determines substrate selectivity and partial processing. Proc. Natl. Acad. Sci. USA 102:1390–95 [Google Scholar]
  50. Khushoo A, Yang Z, Johnson AE, Skach WR. 50.  2011. Ligand-driven vectorial folding of ribosome-bound human CFTR NBD1. Mol. Cell 41:682–92 [Google Scholar]
  51. Kim SY, Miller EJ, Frydman J, Moerner WE. 51.  2010. Action of the chaperonin GroEL/ES on a non-native substrate observed with single-molecule FRET. J. Mol. Biol. 401:553–63 [Google Scholar]
  52. Kodera N, Yamamoto D, Ishikawa R, Ando T. 52.  2010. Video imaging of walking myosin V by high-speed atomic force microscopy. Nature 468:72–76 [Google Scholar]
  53. Kosolapov A, Deutsch C. 53.  2009. Tertiary interactions within the ribosomal exit tunnel. Nat. Struct. Mol. Biol. 16:405–11 [Google Scholar]
  54. Kramer G, Boehringer D, Ban N, Bukau B. 54.  2009. The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins. Nat. Struct. Mol. Biol. 16:589–97 [Google Scholar]
  55. Kramers HA. 55.  1940. Brownian motion in a field of force and the diffusion model of chemical reactions. Physica 7:284–304 [Google Scholar]
  56. Li GW, Xie XS. 56.  2011. Central dogma at the single-molecule level in living cells. Nature 475:308–15 [Google Scholar]
  57. Liphardt J, Dumont S, Smith SB, Tinoco I Jr, Bustamante C. 57.  2002. Equilibrium information from nonequilibrium measurements in an experimental test of Jarzynski's equality. Science 296:1832–35 [Google Scholar]
  58. Lu J, Deutsch C. 58.  2005. Folding zones inside the ribosomal exit tunnel. Nat. Struct. Mol. Biol. 12:1123–29 [Google Scholar]
  59. Maillard RA, Chistol G, Sen M, Righini M, Tan J. 59.  et al. 2011. ClpX(P) generates mechanical force to unfold and translocate its protein substrates. Cell 145:459–69 [Google Scholar]
  60. Martin A, Baker TA, Sauer RT. 60.  2005. Rebuilt AAA+ motors reveal operating principles for ATP-fuelled machines. Nature 437:1115–20 [Google Scholar]
  61. Martin A, Baker TA, Sauer RT. 61.  2007. Distinct static and dynamic interactions control ATPase-peptidase communication in a AAA+ protease. Mol. Cell 27:41–52 [Google Scholar]
  62. Martin A, Baker TA, Sauer RT. 62.  2008. Pore loops of the AAA+ ClpX machine grip substrates to drive translocation and unfolding. Nat. Struct. Mol. Biol. 15:1147–51 [Google Scholar]
  63. Martin A, Baker TA, Sauer RT. 63.  2008. Protein unfolding by a AAA+ protease is dependent on ATP-hydrolysis rates and substrate energy landscapes. Nat. Struct. Mol. Biol. 15:139–45 [Google Scholar]
  64. Mashaghi A, Kramer G, Bechtluft P, Zachmann-Brand B, Driessen AJ. 64.  et al. 2013. Reshaping of the conformational search of a protein by the chaperone trigger factor. Nature 500:98–101 [Google Scholar]
  65. Matouschek A, Bustamante C. 65.  2003. Finding a protein's Achilles heel. Nat. Struct. Biol. 10:674–76 [Google Scholar]
  66. Mickler M, Dima RI, Dietz H, Hyeon C, Thirumalai D, Rief M. 66.  2007. Revealing the bifurcation in the unfolding pathways of GFP by using single-molecule experiments and simulations. Proc. Natl. Acad. Sci. USA 104:20268–73 [Google Scholar]
  67. Mickler M, Hessling M, Ratzke C, Buchner J, Hugel T. 67.  2009. The large conformational changes of Hsp90 are only weakly coupled to ATP hydrolysis. Nat. Struct. Mol. Biol. 16:281–86 [Google Scholar]
  68. Moffitt JR, Chemla YR, Izhaky D, Bustamante C. 68.  2006. Differential detection of dual traps improves the spatial resolution of optical tweezers. Proc. Natl. Acad. Sci. USA 103:9006–11 [Google Scholar]
  69. Moffitt JR, Chemla YR, Smith SB, Bustamante C. 69.  2008. Recent advances in optical tweezers. Annu. Rev. Biochem. 77:205–28 [Google Scholar]
  70. O'Brien EP, Christodoulou J, Vendruscolo M, Dobson CM. 70.  2011. New scenarios of protein folding can occur on the ribosome. J. Am. Chem. Soc. 133:513–26 [Google Scholar]
  71. Oesterhelt F, Oesterhelt D, Pfeiffer M, Engel A, Gaub HE, Müller DJ. 71.  2000. Unfolding pathways of individual bacteriorhodopsins. Science 288:143–46 [Google Scholar]
  72. Pechmann S, Willmund F, Frydman J. 72.  2013. The ribosome as a hub for protein quality control. Mol. Cell 49:411–21 [Google Scholar]
  73. Pedersen S. 73.  1984. Escherichia coli ribosomes translate in vivo with variable rate. EMBO J. 3:2895–98 [Google Scholar]
  74. Perez-Jimenez R, Garcia-Manyes S, Ainavarapu SR, Fernandez JM. 74.  2006. Mechanical unfolding pathways of the enhanced yellow fluorescent protein revealed by single molecule force spectroscopy. J. Biol. Chem. 281:40010–14 [Google Scholar]
  75. Petrov A, Chen J, O'Leary S, Tsai A, Puglisi JD. 75.  2012. Single-molecule analysis of translational dynamics. Cold Spring Harb. Perspect. Biol. 4:a011551 [Google Scholar]
  76. Qu X, Wen JD, Lancaster L, Noller HF, Bustamante C, Tinoco I Jr. 76.  2011. The ribosome uses two active mechanisms to unwind messenger RNA during translation. Nature 475:118–21 [Google Scholar]
  77. Ratzke C, Berkemeier F, Hugel T. 77.  2012. Heat shock protein 90's mechanochemical cycle is dominated by thermal fluctuations. Proc. Natl. Acad. Sci. USA 109:161–66 [Google Scholar]
  78. Ratzke C, Mickler M, Hellenkamp B, Buchner J, Hugel T. 78.  2010. Dynamics of heat shock protein 90 C-terminal dimerization is an important part of its conformational cycle. Proc. Natl. Acad. Sci. USA 107:16101–6 [Google Scholar]
  79. Rodrigo-Brenni MC, Hegde RS. 79.  2012. Design principles of protein biosynthesis-coupled quality control. Dev. Cell 23:896–907 [Google Scholar]
  80. Sauer RT, Baker TA. 80.  2011. AAA+ proteases: ATP-fueled machines of protein destruction. Annu. Rev. Biochem. 80:587–612 [Google Scholar]
  81. Sauer RT, Bolon DN, Burton BM, Burton RE, Flynn JM. 81.  et al. 2004. Sculpting the proteome with AAA+ proteases and disassembly machines. Cell 119:9–18 [Google Scholar]
  82. Siddiqui SM, Sauer RT, Baker TA. 82.  2004. Role of the processing pore of the ClpX AAA+ ATPase in the recognition and engagement of specific protein substrates. Genes Dev. 18:369–74 [Google Scholar]
  83. Shank EA, Cecconi C, Dill JW, Marqusee S, Bustamante C. 83.  2010. The folding cooperativity of a protein is controlled by its chain topology. Nature 465:637–40 [Google Scholar]
  84. Sharma S, Hoskins JR, Wickner S. 84.  2005. Binding and degradation of heterodimeric substrates by ClpAP and ClpXP. J. Biol. Chem. 280:5449–55 [Google Scholar]
  85. Smith SB, Cui Y, Bustamante C. 85.  2003. Optical-trap force transducer that operates by direct measurement of light momentum. Methods Enzymol. 361:134–62 [Google Scholar]
  86. Stigler J, Ziegler F, Gieseke A, Gebhardt JC, Rief M. 86.  2011. The complex folding network of single calmodulin molecules. Science 334:512–16 [Google Scholar]
  87. Szyk A, Maurizi MR. 87.  2006. Crystal structure at 1.9 Å of E. coli ClpP with a peptide covalently bound at the active site. J. Struct. Biol. 156:165–74 [Google Scholar]
  88. Takei Y, Iizuka R, Ueno T, Funatsu T. 88.  2012. Single-molecule observation of protein folding in symmetric GroEL-(GroES)2 complexes. J. Biol. Chem. 287:41118–25 [Google Scholar]
  89. Tinoco I Jr, Gonzalez RL Jr. 89.  2011. Biological mechanisms, one molecule at a time. Genes Dev 25:1205–31 [Google Scholar]
  90. Too PH, Erales J, Simen JD, Marjanovic A, Coffino P. 90.  2013. Slippery substrates impair function of a bacterial protease ATPase by unbalancing translocation versus exit. J. Biol. Chem. 288:13243–57 [Google Scholar]
  91. Tu GF, Reid GE, Zhang JG, Moritz RL, Simpson RJ. 91.  1995. C-terminal extension of truncated recombinant proteins in Escherichia coli with a 10Sa RNA decapeptide. J Biol. Chem. 270:9322–26 [Google Scholar]
  92. Weinkam P, Pletneva EV, Gray HB, Winkler JR, Wolynes PG. 92.  2009. Electrostatic effects on funneled landscapes and structural diversity in denatured protein ensembles. Proc. Natl. Acad. Sci. USA 106:1796–801 [Google Scholar]
  93. Wen JD, Lancaster L, Hodges C, Zeri AC, Yoshimura SH. 93.  et al. 2008. Following translation by single ribosomes one codon at a time. Nature 452:598–603 [Google Scholar]
  94. Wilson DN, Beckmann R. 94.  2011. The ribosomal tunnel as a functional environment for nascent polypeptide folding and translational stalling. Curr. Opin. Struct. Biol. 21:274–82 [Google Scholar]
  95. Woolhead CA, Johnson AE, Bernstein HD. 95.  2006. Translation arrest requires two-way communication between a nascent polypeptide and the ribosome. Mol. Cell 22:587–98 [Google Scholar]
  96. Xu AJ, Springer TA. 96.  2012. Calcium stabilizes the von Willebrand factor A2 domain by promoting refolding. Proc. Natl. Acad. Sci. USA 109:3742–47 [Google Scholar]
  97. Zaher HS, Green R. 97.  2009. Fidelity at the molecular level: lessons from protein synthesis. Cell 136:746–62 [Google Scholar]
  98. Zhang G, Ignatova Z. 98.  2011. Folding at the birth of the nascent chain: coordinating translation with co-translational folding. Curr. Opin. Struct. Biol. 21:25–31 [Google Scholar]
  99. Zhou HX, Dill KA. 99.  2001. Stabilization of proteins in confined spaces. Biochemistry 40:11289–93 [Google Scholar]
/content/journals/10.1146/annurev-biophys-051013-022811
Loading
Mechanisms of Cellular Proteostasis: Insights from Single-Molecule Approaches
Annual Review of Biophysics 43, 119 (2014); https://doi.org/10.1146/annurev-biophys-051013-022811
/content/journals/10.1146/annurev-biophys-051013-022811
/content/journals/10.1146/annurev-biophys-051013-022811
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited 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