Skip to main content
SpringerLink
Log in

Functions of Ribosome-Associated Chaperones and their Interaction Network

  • Chapter
  • First Online:
The Molecular Chaperones Interaction Networks in Protein Folding and Degradation

Part of the book series: Interactomics and Systems Biology ((INTERACTOM,volume 1))

  • 1456 Accesses

Abstract

Cells coordinate chaperones at the exit site of the ribosome. Albeit the types and mechanisms of ribosome-associated chaperones differ in the three kingdoms of life, they all share the ability to protect nascent polypeptides from off pathways such as aggregation and degradation and, at least in some cases, support initial folding steps of newly synthesized proteins. Recent progress was made in understanding the nascent interactome of these ribosome-associated chaperones. While the bacteria-specific chaperone trigger factor (TF) binds to almost every nascent polypeptide made by ribosomes except for membrane proteins, the substrate pool of the two eukaryotic ribosome-associated chaperone systems, nascent polypeptide-associated complex (NAC) and ribosome-associated complex (RAC), is more distinct.

Interestingly, there is culminating evidence that these chaperones also display important functions off the ribosome, e.g., in the biogenesis of ribosomal subunits and in protein aggregation under proteotoxic stress conditions. In this chapter, we will discuss the functions of these chaperones with regard to their broad substrate pools.

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 EPUB and 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

References

  1. Hartl FU, Hayer-Hartl M (2009) Converging concepts of protein folding in vitro and in vivo. Nat Struct Mol Biol 16(6):574–581. doi:10.1038/nsmb.1591

    CAS  PubMed  Google Scholar 

  2. Hartl FU, Bracher A, Hayer-Hartl M (2011) Molecular chaperones in protein folding and proteostasis. Nature 475(7356):324–332. doi:10.1038/nature10317

    CAS  PubMed  Google Scholar 

  3. Bukau B, Deuerling E, Pfund C, Craig EA (2000) Getting newly synthesized proteins into shape. Cell 101(2):119–122. doi:10.1016/S0092-8674(00)80806-5

    CAS  PubMed  Google Scholar 

  4. Preissler S, Deuerling E (2012) Ribosome-associated chaperones as key players in proteostasis. Trends Biochem Sci 37(7):274–283. doi:10.1016/j.tibs.2012.03.002

    CAS  PubMed  Google Scholar 

  5. Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295(5561):1852–1858. doi:10.1126/science.1068408

    CAS  PubMed  Google Scholar 

  6. Maier T, Ferbitz L, Deuerling E, Ban N (2005) A cradle for new proteins: trigger factor at the ribosome. Curr Opin Struct Biol 15(2):204–212. doi:10.1016/j.sbi.2005.03.005

    CAS  PubMed  Google Scholar 

  7. Hoffmann A, Bukau B, Kramer G (2010) Structure and function of the molecular chaperone trigger factor. Biochim Biophys Acta 1803(6):650–661. doi:10.1016/j.bbamcr.2010.01.017

    CAS  PubMed  Google Scholar 

  8. Hoffmann A, Becker AH, Zachmann-Brand B, Deuerling E, Bukau B, Kramer G (2012) Concerted action of the ribosome and the associated chaperone trigger factor confines nascent polypeptide folding. Mol Cell 48(1):63–74. doi:10.1016/j.molcel.2012.07.018

    CAS  PubMed  Google Scholar 

  9. Ferbitz L, Maier T, Patzelt H, Bukau B, Deuerling E, Ban N (2004) Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins. Nature 431(7008):590–596. doi:10.1038/nature02899

    CAS  PubMed  Google Scholar 

  10. Gautschi M, Lilie H, Funfschilling U, Mun A, Ross S, Lithgow T, Rucknagel P, Rospert S (2001) RAC, a stable ribosome-associated complex in yeast formed by the DnaK-DnaJ homologs Ssz1p and Zuo. Proc Natl Acad Sci U S A 98(7):3762–3767. doi:10.1073/pnas.071057198

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Gautschi M, Mun A, Ross S, Rospert S (2002) A functional chaperone triad on the yeast ribosome. Proc Natl Acad Sci U S A 99(7):4209–4214. doi:10.1073/pnas.062048599

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Stoller G, Rucknagel KP, Nierhaus KH, Schmid FX, Fischer G, Rahfeld JU (1995) A ribosome-associated peptidyl-prolyl cis/trans isomerase identified as the trigger factor. EMBO J 14(20):4939–4948

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Kramer G, Rauch T, Rist W, Vorderwulbecke S, Patzelt H, Schulze-Specking A, Ban N, Deuerling E, Bukau B (2002) L23 protein functions as a chaperone docking site on the ribosome. Nature 419(6903):171–174. doi:10.1038/nature01047

    CAS  PubMed  Google Scholar 

  14. Stoller G, Tradler T, Rucknagel KP, Rahfeld JU, Fischer G (1996) An 11.8 kDa proteolytic fragment of the E. coli trigger factor represents the domain carrying the peptidyl-prolyl cis/trans isomerase activity. FEBS Lett 384(2):117–122

    CAS  PubMed  Google Scholar 

  15. Gupta R, Lakshmipathy SK, Chang HC, Etchells SA, Hartl FU (2010) Trigger factor lacking the PPIase domain can enhance the folding of eukaryotic multi-domain proteins in Escherichia coli. FEBS Lett 584(16):3620–3624. doi:10.1016/j.febslet.2010.07.036

    CAS  PubMed  Google Scholar 

  16. Liu CP, Zhou QM, Fan DJ, Zhou JM (2010) PPIase domain of trigger factor acts as auxiliary chaperone site to assist the folding of protein substrates bound to the crevice of trigger factor. Int J Biochem Cell Biol 42(6):890–901. doi:10.1016/j.biocel.2010.01.019

    PubMed  Google Scholar 

  17. Kramer G, Patzelt H, Rauch T, Kurz TA, Vorderwulbecke S, Bukau B, Deuerling E (2004) Trigger factor peptidyl-prolyl cis/trans isomerase activity is not essential for the folding of cytosolic proteins in Escherichia coli. J Biol Chem 279(14):14165–14170. doi:10.1074/jbc.M313635200

    CAS  PubMed  Google Scholar 

  18. Merz F, Boehringer D, Schaffitzel C, Preissler S, Hoffmann A, Maier T, Rutkowska A, Lozza J, Ban N, Bukau B, Deuerling E (2008) Molecular mechanism and structure of Trigger Factor bound to the translating ribosome. Embo J 27(11):1622–1632. doi:10.1038/emboj.2008.89

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Martinez-Hackert E, Hendrickson WA (2009) Promiscuous substrate recognition in folding and assembly activities of the trigger factor chaperone. Cell 138(5):923–934. doi:10.1016/j.cell.2009.07.044

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Rutkowska A, Mayer MP, Hoffmann A, Merz F, Zachmann-Brand B, Schaffitzel C, Ban N, Deuerling E, Bukau B (2008) Dynamics of trigger factor interaction with translating ribosomes. J Biol Chem 283(7):4124–4132. doi:10.1074/jbc.M708294200

    CAS  PubMed  Google Scholar 

  21. Hesterkamp T, Deuerling E, Bukau B (1997) The amino-terminal 118 amino acids of Escherichia coli trigger factor constitute a domain that is necessary and sufficient for binding to ribosomes. J Biol Chem 272(35):21865–21871

    CAS  PubMed  Google Scholar 

  22. Patzelt H, Kramer G, Rauch T, Schonfeld HJ, Bukau B, Deuerling E (2002) Three-state equilibrium of Escherichia coli trigger factor. Biol Chem 383(10):1611–1619. doi:10.1515/BC.2002.182

    PubMed  Google Scholar 

  23. Zarnt T, Tradler T, Stoller G, Scholz C, Schmid FX, Fischer G (1997) Modular structure of the trigger factor required for high activity in protein folding. J Mol Biol 271(5):827–837. doi:10.1006/jmbi.1997.1206

    CAS  PubMed  Google Scholar 

  24. Raine A, Lovmar M, Wikberg J, Ehrenberg M (2006) Trigger factor binding to ribosomes with nascent peptide chains of varying lengths and sequences. J Biol Chem 281(38):28033–28038. doi:10.1074/jbc.M605753200

    CAS  PubMed  Google Scholar 

  25. Maier R, Eckert B, Scholz C, Lilie H, Schmid FX (2003) Interaction of trigger factor with the ribosome. J Mol Biol 326(2):585–592

    CAS  PubMed  Google Scholar 

  26. Kaiser CM, Chang HC, Agashe VR, Lakshmipathy SK, Etchells SA, Hayer-Hartl M, Hartl FU, Barral JM (2006) Real-time observation of trigger factor function on translating ribosomes. Nature 444(7118):455–460. doi:10.1038/nature05225

    CAS  PubMed  Google Scholar 

  27. Oh E, Becker AH, Sandikci A, Huber D, Chaba R, Gloge F, Nichols RJ, Typas A, Gross CA, Kramer G, Weissman JS, Bukau B (2011) Selective ribosome profiling reveals the cotranslational chaperone action of trigger factor in vivo. Cell 147(6):1295–1308. doi:10.1016/j.cell.2011.10.044

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Kramer G, Boehringer D, Ban N, Bukau B (2009) The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins. Nat Struct Mol Biol 16(6):589–597. doi:10.1038/nsmb.1614

    CAS  PubMed  Google Scholar 

  29. Sandikci A, Gloge F, Martinez M, Mayer MP, Wade R, Bukau B, Kramer G (2013) Dynamic enzyme docking to the ribosome coordinates N-terminal processing with polypeptide folding. Nat Struct Mol Biol 20(7):843–850. doi:10.1038/nsmb.2615

    CAS  PubMed  Google Scholar 

  30. Lakshmipathy SK, Gupta R, Pinkert S, Etchells SA, Hartl FU (2010) Versatility of trigger factor interactions with ribosome-nascent chain complexes. J Biol Chem 285(36):27911–27923. doi:10.1074/jbc.M110.134163

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Crooke E, Wickner W (1987) Trigger factor: a soluble protein that folds pro-OmpA into a membrane-assembly-competent form. Proc Natl Acad Sci U S A 84(15):5216–5220

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Deuerling E, Schulze-Specking A, Tomoyasu T, Mogk A, Bukau B (1999) Trigger factor and DnaK cooperate in folding of newly synthesized proteins. Nature 400(6745):693–696. doi:10.1038/23301

    CAS  PubMed  Google Scholar 

  33. Deuerling E, Patzelt H, Vorderwulbecke S, Rauch T, Kramer G, Schaffitzel E, Mogk A, Schulze-Specking A, Langen H, Bukau B (2003) Trigger factor and DnaK possess overlapping substrate pools and binding specificities. Mol Microbiol 47(5):1317–1328

    CAS  PubMed  Google Scholar 

  34. Teter SA, Houry WA, Ang D, Tradler T, Rockabrand D, Fischer G, Blum P, Georgopoulos C, Hartl FU (1999) Polypeptide flux through bacterial Hsp70: DnaK cooperates with trigger factor in chaperoning nascent chains. Cell 97(6):755–765

    CAS  PubMed  Google Scholar 

  35. Agashe VR, Guha S, Chang HC, Genevaux P, Hayer-Hartl M, Stemp M, Georgopoulos C, Hartl FU, Barral JM (2004) Function of trigger factor and DnaK in multidomain protein folding: increase in yield at the expense of folding speed. Cell 117(2):199–209

    CAS  PubMed  Google Scholar 

  36. Patzelt H, Rudiger S, Brehmer D, Kramer G, Vorderwulbecke S, Schaffitzel E, Waitz A, Hesterkamp T, Dong L, Schneider-Mergener J, Bukau B, Deuerling E (2001) Binding specificity of Escherichia coli trigger factor. Proc Natl Acad Sci U S A 98(25):14244–14249. doi:10.1073/pnas.261432298

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Hoffmann A, Merz F, Rutkowska A, Zachmann-Brand B, Deuerling E, Bukau B (2006) Trigger factor forms a protective shield for nascent polypeptides at the ribosome. J Biol Chem 281(10):6539–6545. doi:10.1074/jbc.M512345200

    CAS  PubMed  Google Scholar 

  38. Tomic S, Johnson AE, Hartl FU, Etchells SA (2006) Exploring the capacity of trigger factor to function as a shield for ribosome bound polypeptide chains. FEBS Lett 580(1):72–76. doi:10.1016/j.febslet.2005.11.050

    CAS  PubMed  Google Scholar 

  39. Mashaghi A, Kramer G, Bechtluft P, Zachmann-Brand B, Driessen AJ, Bukau B, Tans SJ (2013) Reshaping of the conformational search of a protein by the chaperone trigger factor. Nature 500(7460):98–101. doi:10.1038/nature12293

    CAS  PubMed  Google Scholar 

  40. Becker AH, Oh E, Weissman JS, Kramer G, Bukau B (2013) Selective ribosome profiling as a tool for studying the interaction of chaperones and targeting factors with nascent polypeptide chains and ribosomes. Nat Protoc 8(11):2212–2239. doi:10.1038/nprot.2013.133

    CAS  PubMed  Google Scholar 

  41. Raue U, Oellerer S, Rospert S (2007) Association of protein biogenesis factors at the yeast ribosomal tunnel exit is affected by the translational status and nascent polypeptide sequence. J Biol Chem 282(11):7809–7816. doi:10.1074/jbc.M611436200

    CAS  PubMed  Google Scholar 

  42. Wiedmann B, Sakai H, Davis TA, Wiedmann M (1994) A protein complex required for signal-sequence-specific sorting and translocation. Nature 370(6489):434–440. doi:10.1038/370434a0

    CAS  PubMed  Google Scholar 

  43. Beatrix B, Sakai H, Wiedmann M (2000) The alpha and beta subunit of the nascent polypeptide-associated complex have distinct functions. J Biol Chem 275(48):37838–37845. doi:10.1074/jbc.M006368200

    CAS  PubMed  Google Scholar 

  44. Reimann B, Bradsher J, Franke J, Hartmann E, Wiedmann M, Prehn S, Wiedmann B (1999) Initial characterization of the nascent polypeptide-associated complex in yeast. Yeast 15(5):397–407. doi:10.1002/(SICI)1097-0061(19990330)15:5<397::AID-YEA384>3.0.CO;2-U

    CAS  PubMed  Google Scholar 

  45. Wang S, Sakai H, Wiedmann M (1995) NAC covers ribosome-associated nascent chains thereby forming a protective environment for regions of nascent chains just emerging from the peptidyl transferase center. J Cell Biol 130(3):519–528

    CAS  PubMed  Google Scholar 

  46. Lauring B, Wang S, Sakai H, Davis TA, Wiedmann B, Kreibich G, Wiedmann M (1995) Nascent-polypeptide-associated complex: a bridge between ribosome and cytosol. Cold Spring Harb Symp Quant Biol 60:47–56

    CAS  PubMed  Google Scholar 

  47. Rospert S, Dubaquie Y, Gautschi M (2002) Nascent-polypeptide-associated complex. Cell Mol Life Sci 59(10):1632–1639

    CAS  PubMed  Google Scholar 

  48. Liu Y, Hu Y, Li X, Niu L, Teng M (2010) The crystal structure of the human nascent polypeptide-associated complex domain reveals a nucleic acid-binding region on the NACA subunit. BioChemistry 49(13):2890–2896. doi:10.1021/bi902050p

    CAS  PubMed  Google Scholar 

  49. Wang L, Zhang W, Zhang XC, Li X, Rao Z (2010) Crystal structures of NAC domains of human nascent polypeptide-associated complex (NAC) and its alphaNAC subunit. Protein Cell 1(4):406–416. doi:10.1007/s13238-010-0049-3

    CAS  PubMed  Google Scholar 

  50. Spreter T, Pech M, Beatrix B (2005) The crystal structure of archaeal nascent polypeptide-associated complex (NAC) reveals a unique fold and the presence of a ubiquitin-associated domain. J Biol Chem 280(16):15849–15854. doi:10.1074/jbc.M500160200

    CAS  PubMed  Google Scholar 

  51. Hurley JH, Lee S, Prag G (2006) Ubiquitin-binding domains. Biochem J 399(3):361–372. doi:10.1042/BJ20061138

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Madura K (2002) The ubiquitin-associated (UBA) domain: on the path from prudence to prurience. Cell Cycle 1(4):235–244

    CAS  PubMed  Google Scholar 

  53. Searle MS, Garner TP, Strachan J, Long J, Adlington J, Cavey JR, Shaw B, Layfield R (2012) Structural insights into specificity and diversity in mechanisms of ubiquitin recognition by ubiquitin-binding domains. Biochem Soc Trans 40(2):404–408. doi:10.1042/BST20110729

    CAS  PubMed  Google Scholar 

  54. Su V, Lau AF (2009) Ubiquitin-like and ubiquitin-associated domain proteins: significance in proteasomal degradation. Cell Mol Life Sci 66(17):2819–2833. doi:10.1007/s00018-009-0048-9

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Wegrzyn RD, Hofmann D, Merz F, Nikolay R, Rauch T, Graf C, Deuerling E (2006) A conserved motif is prerequisite for the interaction of NAC with ribosomal protein L23 and nascent chains. J Biol Chem 281(5):2847–2857. doi:10.1074/jbc.M511420200

    CAS  PubMed  Google Scholar 

  56. Pech M, Spreter T, Beckmann R, Beatrix B (2010) Dual binding mode of the nascent polypeptide-associated complex reveals a novel universal adapter site on the ribosome. J Biol Chem 285(25):19679–19687. doi:10.1074/jbc.M109.092536

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Zhang Y, Berndt U, Golz H, Tais A, Oellerer S, Wolfle T, Fitzke E, Rospert S (2012) NAC functions as a modulator of SRP during the early steps of protein targeting to the endoplasmic reticulum. Mol Biol Cell 23(16):3027–3040. doi:10.1091/mbc.E12-02-0112

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Lauring B, Kreibich G, Weidmann M (1995) The intrinsic ability of ribosomes to bind to endoplasmic reticulum membranes is regulated by signal recognition particle and nascent-polypeptide-associated complex. Proc Natl Acad Sci U S A 92(21):9435–9439

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Lauring B, Sakai H, Kreibich G, Wiedmann M (1995) Nascent polypeptide-associated complex protein prevents mistargeting of nascent chains to the endoplasmic reticulum. Proc Natl Acad Sci U S A 92(12):5411–5415

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Moller I, Beatrix B, Kreibich G, Sakai H, Lauring B, Wiedmann M (1998) Unregulated exposure of the ribosomal M-site caused by NAC depletion results in delivery of non-secretory polypeptides to the Sec61 complex. FEBS Lett 441(1):1–5

    CAS  PubMed  Google Scholar 

  61. Moller I, Jung M, Beatrix B, Levy R, Kreibich G, Zimmermann R, Wiedmann M, Lauring B (1998) A general mechanism for regulation of access to the translocon: competition for a membrane attachment site on ribosomes. Proc Natl Acad Sci U S A 95(23):13425–13430

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Powers T, Walter P (1996) The nascent polypeptide-associated complex modulates interactions between the signal recognition particle and the ribosome. Curr Biol 6(3):331–338

    CAS  PubMed  Google Scholar 

  63. Raden D, Gilmore R (1998) Signal recognition particle-dependent targeting of ribosomes to the rough endoplasmic reticulum in the absence and presence of the nascent polypeptide-associated complex. Mol Biol Cell 9(1):117–130

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Wickner W (1995) The nascent-polypeptide-associated complex: having a “NAC” for fidelity in translocation. Proc Natl Acad Sci U S A 92(21):9433–9434

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Kim SH, Shim KS, Lubec G (2002) Human brain nascent polypeptide-associated complex alpha subunit is decreased in patients with Alzheimer’ s disease and Down syndrome. J Investig Med 50(4):293–301

    CAS  PubMed  Google Scholar 

  66. Thiede B, Dimmler C, Siejak F, Rudel T (2001) Predominant identification of RNA-binding proteins in Fas-induced apoptosis by proteome analysis. J Biol Chem 276(28):26044–26050. doi:10.1074/jbc.M101062200

    CAS  PubMed  Google Scholar 

  67. Bloss TA, Witze ES, Rothman JH (2003) Suppression of CED-3-independent apoptosis by mitochondrial betaNAC in Caenorhabditis elegans. Nature 424(6952):1066–1071. doi:10.1038/nature01920

    CAS  PubMed  Google Scholar 

  68. Quelo I, Hurtubise M, St-Arnaud R (2002) alphaNAC requires an interaction with c-Jun to exert its transcriptional coactivation. Gene Expr 10(5-6):255–262

    CAS  PubMed  Google Scholar 

  69. Yotov WV, Moreau A, St-Arnaud R (1998) The alpha chain of the nascent polypeptide-associated complex functions as a transcriptional coactivator. Mol Cell Biol 18(3):1303–1311

    CAS  PubMed Central  PubMed  Google Scholar 

  70. Yotov WV, St-Arnaud R (1996) Differential splicing-in of a proline-rich exon converts alphaNAC into a muscle-specific transcription factor. Genes Dev 10(14):1763–1772

    CAS  PubMed  Google Scholar 

  71. Moreau A, Yotov WV, Glorieux FH, St-Arnaud R (1998) Bone-specific expression of the alpha chain of the nascent polypeptide-associated complex, a coactivator potentiating c-Jun-mediated transcription. Mol Cell Biol 18(3):1312–1321

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Markesich DC, Gajewski KM, Nazimiec ME, Beckingham K (2000) bicaudal encodes the Drosophila beta NAC homolog, a component of the ribosomal translational machinery*. Development 127(3):559–572

    CAS  PubMed  Google Scholar 

  73. Deng JM, Behringer RR (1995) An insertional mutation in the BTF3 transcription factor gene leads to an early postimplantation lethality in mice. Transgenic Res 4(4):264–269

    CAS  PubMed  Google Scholar 

  74. Deuerling E, Bukau B (2004) Chaperone-assisted folding of newly synthesized proteins in the cytosol. Crit Rev Biochem Mol Biol 39(5-6):261–277. doi:10.1080/10409230490892496

    CAS  PubMed  Google Scholar 

  75. Pechmann S, Willmund F, Frydman J (2013) The ribosome as a hub for protein quality control. Mol Cell 49(3):411–421. doi:10.1016/j.molcel.2013.01.020

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Wegrzyn RD, Deuerling E (2005) Molecular guardians for newborn proteins: ribosome-associated chaperones and their role in protein folding. Cell Mol Life Sci 62(23):2727–2738. doi:10.1007/s00018-005-5292-z

    CAS  PubMed  Google Scholar 

  77. Koplin A, Preissler S, Ilina Y, Koch M, Scior A, Erhardt M, Deuerling E (2010) A dual function for chaperones SSB-RAC and the NAC nascent polypeptide-associated complex on ribosomes. J Cell Biol 189(1):57–68. doi:10.1083/jcb.200910074

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Kirstein-Miles J, Scior A, Deuerling E, Morimoto RI (2013) The nascent polypeptide-associated complex is a key regulator of proteostasis. EMBO J 32(10):1451–1468. doi:10.1038/emboj.2013.87

    CAS  PubMed Central  PubMed  Google Scholar 

  79. del Alamo M, Hogan DJ, Pechmann S, Albanese V, Brown PO, Frydman J (2011) Defining the specificity of cotranslationally acting chaperones by systematic analysis of mRNAs associated with ribosome-nascent chain complexes. PLoS Biol 9(7):e1001100. doi:10.1371/journal.pbio.1001100

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Duttler S, Pechmann S, Frydman J (2013) Principles of cotranslational ubiquitination and quality control at the ribosome. Mol Cell 50(3):379–393. doi:10.1016/j.molcel.2013.03.010

    CAS  PubMed  Google Scholar 

  81. Huang P, Gautschi M, Walter W, Rospert S, Craig EA (2005) The Hsp70 Ssz1 modulates the function of the ribosome-associated J-protein Zuo1. Nat Struct Mol Biol 12(6):497–504. doi:10.1038/nsmb942

    CAS  PubMed  Google Scholar 

  82. Pfund C, Lopez-Hoyo N, Ziegelhoffer T, Schilke BA, Lopez-Buesa P, Walter WA, Wiedmann M, Craig EA (1998) The molecular chaperone Ssb from Saccharomyces cerevisiae is a component of the ribosome-nascent chain complex. EMBO J 17(14):3981–3989. doi:10.1093/emboj/17.14.3981

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Conz C, Otto H, Peisker K, Gautschi M, Wolfle T, Mayer MP, Rospert S (2007) Functional characterization of the atypical Hsp70 subunit of yeast ribosome-associated complex. J Biol Chem 282(47):33977–33984. doi:10.1074/jbc.M706737200

    CAS  PubMed  Google Scholar 

  84. Leidig C, Bange G, Kopp J, Amlacher S, Aravind A, Wickles S, Witte G, Hurt E, Beckmann R, Sinning I (2013) Structural characterization of a eukaryotic chaperone-the ribosome-associated complex. Nat Struct Mol Biol 20(1):23–28. doi:10.1038/nsmb.2447

    CAS  PubMed  Google Scholar 

  85. Peisker K, Braun D, Wolfle T, Hentschel J, Funfschilling U, Fischer G, Sickmann A, Rospert S (2008) Ribosome-associated complex binds to ribosomes in close proximity of Rpl31 at the exit of the polypeptide tunnel in yeast. Mol Biol Cell 19(12):5279–5288. doi:10.1091/mbc.E08-06-0661

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Yan W, Schilke B, Pfund C, Walter W, Kim S, Craig EA (1998) Zuo, a ribosome-associated DnaJ molecular chaperone. EMBO J 17(16):4809–4817. doi:10.1093/emboj/17.16.4809

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Fiaux J, Horst J, Scior A, Preissler S, Koplin A, Bukau B, Deuerling E (2010) Structural analysis of the ribosome-associated complex (RAC) reveals an unusual Hsp70/Hsp40 interaction. J Biol Chem 285(5):3227–3234. doi:10.1074/jbc.M109.075804

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Kim SY, Craig EA (2005) Broad sensitivity of Saccharomyces cerevisiae lacking ribosome-associated chaperone ssb or zuo1 to cations, including aminoglycosides. Eukaryot Cell 4(1):82–89. doi:10.1128/EC.4.1.82-89.2005

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Nelson RJ, Ziegelhoffer T, Nicolet C, Werner-Washburne M, Craig EA (1992) The translation machinery and 70 kd heat shock protein cooperate in protein synthesis. Cell 71(1):97–105

    CAS  PubMed  Google Scholar 

  90. Hundley H, Eisenman H, Walter W, Evans T, Hotokezaka Y, Wiedmann M, Craig E (2002) The in vivo function of the ribosome-associated Hsp70, Ssz1, does not require its putative peptide-binding domain. Proc Natl Acad Sci U S A 99(7):4203–4208. doi:10.1073/pnas.062048399

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Rauch T, Hundley HA, Pfund C, Wegrzyn RD, Walter W, Kramer G, Kim SY, Craig EA, Deuerling E (2005) Dissecting functional similarities of ribosome-associated chaperones from Saccharomyces cerevisiae and Escherichia coli. Mol Microbiol 57(2):357–365. doi:10.1111/j.1365-2958.2005.04690.x

    CAS  PubMed  Google Scholar 

  92. Willmund F, del Alamo M, Pechmann S, Chen T, Albanese V, Dammer EB, Peng J, Frydman J (2013) The cotranslational function of ribosome-associated Hsp70 in eukaryotic protein homeostasis. Cell 152(1-2):196–209. doi:10.1016/j.cell.2012.12.001

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Shulga N, James P, Craig EA, Goldfarb DS (1999) A nuclear export signal prevents Saccharomyces cerevisiae Hsp70 Ssb1p from stimulating nuclear localization signal-directed nuclear transport. J Biol Chem 274(23):16501–16507

    CAS  PubMed  Google Scholar 

  94. Zhang S, Lockshin C, Herbert A, Winter E, Rich A (1992) Zuo, a putative Z-DNA binding protein in Saccharomyces cerevisiae. EMBO J 11(10):3787–3796

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Hundley HA, Walter W, Bairstow S, Craig EA (2005) Human Mpp11 J protein: ribosome-tethered molecular chaperones are ubiquitous. Science 308(5724):1032–1034. doi:10.1126/science.1109247

    CAS  PubMed  Google Scholar 

  96. Jaiswal H, Conz C, Otto H, Wolfle T, Fitzke E, Mayer MP, Rospert S (2011) The chaperone network connected to human ribosome-associated complex. Mol Cell Biol 31(6):1160–1173. doi:10.1128/MCB.00986-10

    CAS  PubMed Central  PubMed  Google Scholar 

  97. Otto H, Conz C, Maier P, Wolfle T, Suzuki CK, Jeno P, Rucknagel P, Stahl J, Rospert S (2005) The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex. Proc Natl Acad Sci U S A 102(29):10064–10069. doi:10.1073/pnas.0504400102

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Albanese V, Reissmann S, Frydman J (2010) A ribosome-anchored chaperone network that facilitates eukaryotic ribosome biogenesis. J Cell Biol 189(1):69–81. doi:10.1083/jcb.201001054

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Henras AK, Soudet J, Gerus M, Lebaron S, Caizergues-Ferrer M, Mougin A, Henry Y (2008) The post-transcriptional steps of eukaryotic ribosome biogenesis. Cell Mol Life Sci 65(15):2334–2359. doi:10.1007/s00018-008-8027-0

    CAS  PubMed  Google Scholar 

  100. von Plehwe U, Berndt U, Conz C, Chiabudini M, Fitzke E, Sickmann A, Petersen A, Pfeifer D, Rospert S (2009) The Hsp70 homolog Ssb is essential for glucose sensing via the SNF1 kinase network. Genes Dev 23(17):2102–2115. doi:10.1101/gad.529409

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Ducett JK, Peterson FC, Hoover LA, Prunuske AJ, Volkman BF, Craig EA (2013) Unfolding of the C-terminal domain of the J-protein Zuo1 releases autoinhibition and activates Pdr1-dependent transcription. J Mol Biol 425(1):19–31. doi:10.1016/j.jmb.2012.09.020

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Prunuske AJ, Waltner JK, Kuhn P, Gu B, Craig EA (2012) Role for the molecular chaperones Zuo1 and Ssz1 in quorum sensing via activation of the transcription factor Pdr1. Proc Natl Acad Sci U S A 109(2):472–477. doi:10.1073/pnas.1119184109

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Eisenman HC, Craig EA (2004) Activation of pleiotropic drug resistance by the J-protein and Hsp70-related proteins, Zuo1 and Ssz1. Mol Microbiol 53(1):335–344. doi:10.1111/j.1365-2958.2004.04134.x

    CAS  PubMed  Google Scholar 

  104. Olzscha H, Schermann SM, Woerner AC, Pinkert S, Hecht MH, Tartaglia GG, Vendruscolo M, Hayer-Hartl M, Hartl FU, Vabulas RM (2011) Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions. Cell 144(1):67–78. doi:10.1016/j.cell.2010.11.050

    CAS  PubMed  Google Scholar 

  105. Tyedmers J, Mogk A, Bukau B (2010) Cellular strategies for controlling protein aggregation. Nat Rev Mol Cell Biol 11(11):777–788. doi:10.1038/nrm2993

    CAS  PubMed  Google Scholar 

  106. Kirstein-Miles J, Morimoto RI (2013) Ribosome-associated chaperones act as proteostasis sentinels. Cell Cycle 12(15):2335–2336. doi:10.4161/cc.25703

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, University of Konstanz, Konstanz, Germany

    Annika Scior PhD & Prof. Dr. Elke Deuerling PhD

Authors
  1. Annika Scior PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prof. Dr. Elke Deuerling PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elke Deuerling PhD .

Editor information

Editors and Affiliations

  1. Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada

    Walid A. Houry

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Scior, A., Deuerling, E. (2014). Functions of Ribosome-Associated Chaperones and their Interaction Network. In: Houry, W. (eds) The Molecular Chaperones Interaction Networks in Protein Folding and Degradation. Interactomics and Systems Biology, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1130-1_2

Download citation

Publish with us

Policies and ethics

Search

Navigation