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Folding of newly synthesised proteins in the endoplasmic reticulum

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Chaperones

Part of the book series: Topics in Current Genetics ((TCG,volume 16))

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Abstract

The endoplasmic reticulum (ER) is a membranous compartment that can be found within any nucleated eukaryotic cell. Its job is to oversee the production of all the proteins that the cell secretes, or needs to express at the cell surface or within the secretory pathway itself. The type of proteins that pass through the ER is very varied, ranging from small, secreted peptide hormones, to large cell surface receptors. To the uninitiated, protein folding in the endoplasmic reticulum might seem straightforward. Unfortunately for biology students, but fortunately for researchers, it turns out that protein folding in the ER is a complex business, involving chaperones, quality control machinery and many accessory factors. These molecular helpers make sure that glycoproteins fold properly, and are directed to the right cellular location at the right time. Although many newly synthesised proteins follow a set of common ”rules”, some proteins require specific types of chaperones to assist them. In this review, recent advances in our knowledge of the early stages of ER protein folding will be discussed, focusing on the mammalian ER, but also drawing on examples of work in yeast.

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References

  • 1. Aguzzi A, Heikenwalder M, Miele G (2004) Progress and problems in the biology, diagnostics, and therapeutics of prion diseases. J Clin Invest 114:153-160

    PubMed  CAS  Google Scholar 

  • 2. Alanen HI, Salo KE, Pekkala M, Siekkinen HM, Pirneskoski A, Ruddock LW (2003a) Defining the domain boundaries of the human protein disulfide isomerases. Antioxid Redox Signal 5:367-374

    PubMed  CAS  Google Scholar 

  • 3. Alanen HI, Williamson RA, Howard MJ, Lappi A-K, Jantti HP, Rautio SM, Kellokumpu S, Ruddock LW (2003b) Functional Characterization of ERp18, a new endoplasmic reticulum-located thioredoxin superfamily member. J Biol Chem 278:28912-28920

    PubMed  CAS  Google Scholar 

  • 4. Alberti S, Bohse K, Arndt V, Schmitz A, Hohfeld J (2004) The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator. Mol Biol Cell 15:4003-4010

    PubMed  CAS  Google Scholar 

  • 5. Alberti S, Demand J, Esser C, Emmerich N, Schild H, Hohfeld J (2002) Ubiquitylation of BAG-1 suggests a novel regulatory mechanism during the sorting of chaperone substrates to the proteasome. J Biol Chem 277:45920-45927

    PubMed  CAS  Google Scholar 

  • 6. Andersson H, Garoff H (2003) Lectin-mediated retention of p62 facilitates p62-E1 heterodimerization in endoplasmic reticulum of Semliki Forest virus-infected cells. J Virol 77:6676-6682

    PubMed  Google Scholar 

  • 7. Anelli T, Alessio M, Bachi A, Bergamelli L, Bertoli G, Camerinin S, Mezghrani A, Ruffato E, Simmen T, Sitia R (2003) Thiol-mediated protein retention in the endoplasmic reticulum: the role of ERp44. EMBO J 22:5015-5022

    PubMed  CAS  Google Scholar 

  • 8. Anelli T, Alessio M, Mezghrani A, Simmen T, Talamo F, Bachi A, Sitia R (2002) ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO J 21:835-844

    PubMed  CAS  Google Scholar 

  • 9. Antoniou AN, Ford S, Alphey M, Osborne A, Elliott T, Powis SJ (2002) The oxidoreductase ERp57 efficiently reduces partially folded in preference to fully folded MHC class I molecules. EMBO J 21:2655-2663

    PubMed  CAS  Google Scholar 

  • 10. Avila G, Lee EH, Perez CF, Allen PD, Dirksen RJ (2003) FKBP12 binding to RyR1 modulates excitation-contraction coupling in mouse skeletal myotubes. J Biol Chem 278:22600-22608

    PubMed  CAS  Google Scholar 

  • 11. Bass R, Ruddock LW, Klappa P, Freedman RB (2004) A major fraction of endoplasmic reticulum-located glutathione is present as mixed disulfides with protein. J Biol Chem 279:5257-5262

    PubMed  CAS  Google Scholar 

  • 12. Benayoun B, Esnard-Feve A, Castella S, Courty Y, Esnard F (2001) Rat seminal vesicle FAD-dependent sulfhydryl oxidase. Biochemical characterization and molecular cloning of a member of the new sulfhydryl oxidase/quiescin Q6 gene family. J Biol Chem 276:13830-13837

    PubMed  CAS  Google Scholar 

  • 13. Benham AM, Cabibbo A, Fassio A, Bulleid N, Sitia R, Braakman I (2000) The CXXCXXC motif determines the folding, structure and stability of human Ero1-Lalpha. EMBO J 19:4493-4502

    PubMed  CAS  Google Scholar 

  • 14. Bergman LW, Kuehl WM (1979) Formation of an intrachain disulfide bond on nascent immunoglobulin light chains. J Biol Chem 254:8869-8876

    PubMed  CAS  Google Scholar 

  • 15. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D (2000) Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2:326-332

    PubMed  CAS  Google Scholar 

  • 16. Bogdanov M, Dowhan W (1999) Lipid-assisted Protein Folding. J Biol Chem 274:36827-36830

    PubMed  CAS  Google Scholar 

  • 17. Bottomley MJ, Batten MR, Lumb RA, Bulleid NJ (2001) Quality control in the endoplasmic reticulum. PDI mediates the ER retention of unassembled procollagen C-propeptides. Curr Biol 11:1114-1118

    PubMed  CAS  Google Scholar 

  • 18. Braakman I, Hoover-Litty H, Wagner KR, Helenius A (1991) Folding of influenza hemagglutinin in the endoplasmic reticulum. J Cell Biol 114:401-411

    PubMed  CAS  Google Scholar 

  • 19. Bu G, Geuze H, Strous G, Schwartz A (1995) 39 kDa receptor-associated protein is an ER resident protein and molecular chaperone for LDL receptor-related protein. EMBO J 14:2269-2280

    PubMed  CAS  Google Scholar 

  • 20. Bulleid NJ, Freedman RB (1988) Defective co-translational formation of disulphide bonds in protein disulphide-isomerase-deficient microsomes. Nature 335:649-651

    PubMed  CAS  Google Scholar 

  • 21. Bullough PA, Hughson FM, Skehel JJ, Wiley DC (1994) Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 371:37-43

    PubMed  CAS  Google Scholar 

  • 22. Cabibbo A, Pagani M, Fabbri M, Rocchi M, Farmery MR, Bulleid NJ, Sitia R (2000) ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum. J Biol Chem 275:4827-4833

    PubMed  CAS  Google Scholar 

  • 23. Cannon KS, Cresswell P (2001) Quality control of transmembrane domain assembly in the tetraspanin CD82. EMBO J 20:2443-2453

    PubMed  CAS  Google Scholar 

  • 24. Caramelo JJ, Castro OA, Alonso LG, De Prat-Gay G, Parodi AJ (2003) Inaugural article: UDP-Glc:glycoprotein glucosyltransferase recognizes structured and solvent accessible hydrophobic patches in molten globule-like folding intermediates. Proc Natl Acad Sci USA 100:86-91

    PubMed  CAS  Google Scholar 

  • 25. Chakravarthi S, Bulleid NJ (2004) Glutathione is required to regulate the formation of native disulfide bonds within proteins entering the secretory pathway. J Biol Chem 279:39872-39879

    PubMed  CAS  Google Scholar 

  • 26. Chung KT, Shen Y, Hendershot LM (2002) BAP, a mammalian BiP-associated protein, is a nucleotide exchange factor that regulates the ATPase activity of BiP. J Biol Chem 277:47557-47563

    PubMed  CAS  Google Scholar 

  • 27. Clemons J, William M, Menetret J-F, Akey CW, Rapoport TA (2004) Structural insight into the protein translocation channel. Curr Opin Struct Biol 14:390-396

    PubMed  CAS  Google Scholar 

  • 28. Copeland CS, Zimmer KP, Wagner KR, Healey GA, Mellman I, Helenius A (1988) Folding, trimerization, and transport are sequential events in the biogenesis of influenza virus hemagglutinin. Cell 53:197-209

    PubMed  CAS  Google Scholar 

  • 29. Cresswell P, Bangia N, Dick T, Diedrich G (1999) The nature of the MHC class I peptide loading complex. Immunol Rev 172:21-28

    PubMed  CAS  Google Scholar 

  • 30. Cunnea PM, Miranda-Vizuete A, Bertoli G, Simmen T, Damdimopoulos AE, Hermann S, Leinonen S, Huikko MP, Gustafsson J-A, Sitia R, Spyrou G (2003) ERdj5, an endoplasmic reticulum (ER)-resident protein containing DnaJ and thioredoxin domains, is expressed in secretory cells or following ER stress. J Biol Chem 278:1059-1066

    PubMed  CAS  Google Scholar 

  • 31. Daniels R, Kurowski B, Johnson A, Hebert DN (2003) N-linked glycans direct the cotranslational folding pathway of influenza hemagglutinin. Mol Cell 11:79-90

    PubMed  CAS  Google Scholar 

  • 32. Darby NJ, Kemmink J, Creighton TE (1996) Identifying and characterizing a structural domain of protein disulfide isomerase. Biochemistry 35:10517-10528

    PubMed  CAS  Google Scholar 

  • 33. David V, Hochstenbach F, Rajagopalan S, Brenner M (1993) Interaction with newly synthesized and retained proteins in the endoplasmic reticulum suggests a chaperone function for human integral membrane protein IP90 (calnexin). J Biol Chem 268:9585-9592

    PubMed  CAS  Google Scholar 

  • 34. Dick TP, Bangia N, Peaper DR, Cresswell P (2002) Disulfide bond isomerization and the assembly of MHC class I-peptide complexes. Immunity 16:87-98

    PubMed  CAS  Google Scholar 

  • 35. Dooley CT, Dore TM, Hanson GT, Jackson WC, Remington SJ, Tsien RY (2004) Imaging dynamic redox changes in mammalian cells with green fluorescent protein indicators. J Biol Chem 279:22284-22293

    PubMed  CAS  Google Scholar 

  • 36. Ellgaard L, Helenius A (2003) Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4:181-191

    PubMed  CAS  Google Scholar 

  • 37. Ellgaard L, Riek R, Herrmann T, Guntert P, Braun D, Helenius A, Wuthrich K (2001) NMR structure of the calreticulin P-domain. Proc Natl Acad Sci USA 98:3133-3138

    PubMed  CAS  Google Scholar 

  • 38. Ellis CD, Wang F, Macdiarmid CW, Clark S, Lyons T, Eide DJ (2004) Zinc and the Msc2 zinc transporter protein are required for endoplasmic reticulum function. J Cell Biol 166:325-335

    PubMed  CAS  Google Scholar 

  • 39. Fass D, Blacklow S, Kim PS, Berger JM (1997) Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module. Nature 388:691-693

    PubMed  CAS  Google Scholar 

  • 40. Ferrari DM, Nguyen Van P, Kratzin HD, Soling H-D (1998) ERp28, a human endoplasmic-reticulum-lumenal protein, is a member of the protein disulfide isomerase family but lacks a CXXC thioredoxin-box motif. Eur J Biochem 255:570-579

    PubMed  CAS  Google Scholar 

  • 41. Frand AR, Kaiser CA (1998) The ERO1 gene of yeast is required for oxidation of protein dithiols in the endoplasmic reticulum. Mol Cell 1:161-170

    PubMed  CAS  Google Scholar 

  • 42. Frand AR, Kaiser CA (1999) Ero1p oxidizes protein disulfide isomerase in a pathway for disulfide bond formation in the endoplasmic reticulum. Mol Cell 4:469-477

    PubMed  CAS  Google Scholar 

  • 43. Frand AR, Kaiser CA (2000) Two pairs of conserved cysteines are required for the oxidative activity of Ero1p in protein disulfide bond formation in the endoplasmic reticulum. Mol Biol Cell 11:2833-2843

    PubMed  CAS  Google Scholar 

  • 44. Frickel E-M, Frei P, Bouvier M, Stafford WF, Helenius A, Glockshuber R, Ellgaard L (2004) ERp57 is a multifunctional thiol-disulfide oxidoreductase. J Biol Chem 279:18277-18287

    PubMed  CAS  Google Scholar 

  • 45. Gess B, Hofbauer K-H, Wenger RH, Lohaus C, Meyer HE, Kurtz A (2003) The cellular oxygen tension regulates expression of the endoplasmic oxidoreductase ERO1-Lalpha. Eur J Biochem 270:2228-2235

    PubMed  CAS  Google Scholar 

  • 46. Gierasch LM (1994) Molecular chaperones. Panning for chaperone-binding peptides. Curr Biol 4:173-174

    PubMed  CAS  Google Scholar 

  • 47. Gillece P, Luz JM, Lennarz WJ, De La Cruz FJ, Romisch K (1999) Export of a cysteine-free misfolded secretory protein from the endoplasmic reticulum for degradation requires interaction with protein disulfide isomerase. J Cell Biol 147:1443-1456

    PubMed  CAS  Google Scholar 

  • 48. Gross E, Kastner DB, Kaiser CA, Fass D (2004) Structure of Ero1p, source of disulfide bonds for oxidative protein folding in the cell. Cell 117:601-610

    PubMed  CAS  Google Scholar 

  • 49. Gross E, Sevier CS, Vala A, Kaiser CA, Fass D (2002) A new FAD-binding fold and intersubunit disulfide shuttle in the thiol oxidase Erv2p. Nat Struct Biol 9:61-67

    PubMed  CAS  Google Scholar 

  • 50. Haas IG, Wabl M (1983) Immunoglobulin heavy chain binding protein. Nature 306:387-389

    PubMed  CAS  Google Scholar 

  • 51. Hamman BD, Hendershot LM, Johnson AE (1998) BiP maintains the permeability barrier of the ER membrane by sealing the lumenal end of the translocon pore before and early in translocation. Cell 92:747-758

    PubMed  CAS  Google Scholar 

  • 52. Hammond C, Braakman I, Helenius A (1994) Role of N-linked oligosaccharide recognition, glucose trimming, and calnexin in glycoprotein folding and quality control. Proc Natl Acad Sci USA 91:913-917

    PubMed  CAS  Google Scholar 

  • 53. Haugstetter J, Blicher T, Ellgaard L (2005) Identification and characterisation of a novel thioredoxin-related transmembrane protein of the endoplasmic reticulum. J Biol Chem 280:8371-8380

    PubMed  CAS  Google Scholar 

  • 54. Hebert DN, Zhang J-X, Chen W, Foellmer B, Helenius A (1997) The number and location of glycans on influenza hemagglutinin determine folding and association with calnexin and calreticulin. J Cell Biol 139:613-623

    PubMed  CAS  Google Scholar 

  • 55. Helenius A, Aebi M (2004) Roles of N-linked glycans in the endoplasmic reticulum. Annu Rev Biochem 73:1019-1049

    PubMed  CAS  Google Scholar 

  • 56. Hosoda A, Kimata Y, Tsuru A, Kohno K (2003) JPDI, a novel endoplasmic reticulum-resident protein containing both a BiP-interacting J-domain and thioredoxin-like motifs. J Biol Chem 278:2669-2676

    PubMed  CAS  Google Scholar 

  • 57. Hosokawa N, Wada I, Hasegawa K, Yorihuzi T, Tremblay LO, Herscovics A, Nagata K (2001) A novel ER alpha-mannosidase-like protein accelerates ER-associated degradation. EMBO Rep 2:415-422

    PubMed  CAS  Google Scholar 

  • 58. Hwang C, Sinskey AJ, Lodish HF (1992) Oxidized redox state of glutathione in the endoplasmic reticulum. Science 257:1496-1502

    PubMed  CAS  Google Scholar 

  • 59. Ihara Y, Cohen-Doyle MF, Saito Y, Williams DB (1999) Calnexin discriminates between protein conformational states and functions as a molecular chaperone in vitro. Mol Cell 4:331-341

    PubMed  CAS  Google Scholar 

  • 60. Iwawaki T, Akai R, Kohno K, Miura M (2004) A transgenic mouse model for monitoring endoplasmic reticulum stress. Nat Med 10:98-102

    PubMed  CAS  Google Scholar 

  • 61. Jansens A, Braakman I (2002) Coordinated non-vectorial folding in a newly synthesized multidomain protein. Science 298:2401-2403

    PubMed  CAS  Google Scholar 

  • 62. Johnson AE, Van Waes MA (1999) The translocon: a dynamic gateway at the ER membrane. Annu Rev Cell Dev Biol 15:799-842

    PubMed  Google Scholar 

  • 63. Kemmink J, Darby NJ, Dijkstra K, Nilges M, Creighton TE (1996) Structure determination of the N-terminal thioredoxin-like domain of protein disulfide isomerase using multidimensional heteronuclear 13C/15N NMR spectroscopy. Biochemistry 35:7684-7691

    PubMed  CAS  Google Scholar 

  • 64. Kemmink J, Darby NJ, Dijkstra K, Nilges M, Creighton TE (1997) The folding catalyst protein disulfide isomerase is constructed of active and inactive thioredoxin modules. Curr Biol 7:239-245

    PubMed  CAS  Google Scholar 

  • 65. Kemmink J, Darby NJ, Dijkstra K, Scheek RM, Creighton TE (1995) Nuclear magnetic resonance characterization of the N-terminal thioredoxin-like domain of protein disulfide isomerase. Protein Sci 4:2587-2593

    PubMed  CAS  Google Scholar 

  • 66. Kim P, Arvan P (1995) Calnexin and BiP act as sequential molecular chaperones during thyroglobulin folding in the endoplasmic reticulum. J Cell Biol 128:29-38

    PubMed  CAS  Google Scholar 

  • 67. Kim P, Kwon O, Arvan P (1996) An endoplasmic reticulum storage disease causing congenital goiter with hypothyroidism. J Cell Biol 133:517-527

    PubMed  CAS  Google Scholar 

  • 68. Klappa P, Ruddock LW, Darby NJ, Freedman RB (1998) The b' domain provides the principal peptide-binding site of protein disulfide isomerase but all domains contribute to binding of misfolded proteins. EMBO J 17:927-935

    PubMed  CAS  Google Scholar 

  • 69. Knoblach B, Keller BO, Groenendyk J, Aldred S, Zheng J, Lemire BD, Li L, Michalak M (2003) ERp19 and ERp46, new members of the thioredoxin family of endoplasmic reticulum proteins. Mol Cell Proteomics 2:1104-119

    PubMed  CAS  Google Scholar 

  • 70. Kopito RR (1999) Biosynthesis and degradation of CFTR. Physiol Rev 79:167-173

    Google Scholar 

  • 71. Kuznetsov G, Chen L, Nigam S (1994) Several endoplasmic reticulum stress proteins, including ERp72, interact with thyroglobulin during its maturation. J Biol Chem 269:22990-22995

    PubMed  CAS  Google Scholar 

  • 72. Laboissiere MC, Sturley SL, Raines RT (1995) The essential function of protein-disulfide isomerase is to unscramble non-native disulfide bonds. J Biol Chem 270:28006-28009

    PubMed  CAS  Google Scholar 

  • 73. Lawless MW, Greene CM, Mulgrew A, Taggart CC, O'Neill SJ, McElvaney NG (2004) Activation of endoplasmic reticulum-specific stress responses associated with the conformational disease Z alpha 1-antitrypsin deficiency. J Immunol 172:5722-5726

    PubMed  CAS  Google Scholar 

  • 74. Lemberg MK, Bland FA, Weihofen A, Braud VM, Martoglio B (2001) Intramembrane proteolysis of signal peptides: an essential step in the generation of HLA-E epitopes. J Immunol 167:6441-6446

    PubMed  CAS  Google Scholar 

  • 75. Li Y, Camacho P (2004) Ca2+-dependent redox modulation of SERCA 2b by ERp57. J Cell Biol 164:35-46

    PubMed  CAS  Google Scholar 

  • 76. Liao S, Lin J, Do H, Johnson AE (1997) Both lumenal and cytosolic gating of the aqueous ER translocon pore are regulated from inside the ribosome during membrane protein integration. Cell 90:31-41

    PubMed  CAS  Google Scholar 

  • 77. Linke K, Jakob U (2003) Not every disulfide lasts forever: disulfide bond formation as a redox switch. Antioxid Redox Signal 5:425-434

    PubMed  CAS  Google Scholar 

  • 78. Lisanti MP, Caras IW, Davitz MA, Rodriguez-Boulan E (1989) A glycophospholipid membrane anchor acts as an apical targeting signal in polarized epithelial cells. J Cell Biol 109:2145-2156

    PubMed  CAS  Google Scholar 

  • 79. Loo MA, Jensen TJ, Cui L, Hou Y, Chang XB, Riordan JR (1998) Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome. EMBO J 17:6879-6887

    PubMed  CAS  Google Scholar 

  • 80. Lundstrom J, Holmgren A (1993) Determination of the reduction-oxidation potential of the thioredoxin-like domains of protein disulfide-isomerase from the equilibrium with glutathione and thioredoxin. Biochemistry 32:6649-6655

    PubMed  CAS  Google Scholar 

  • 81. Luo L, Shoichet MS (2004) A photolabile hydrogel for guided three-dimensional cell growth and migration. Nat Mater 3:249-253

    PubMed  CAS  Google Scholar 

  • 82. Ma Q, Guo C, Barnewitz K, Sheldrick GM, Soling HD, Uson I, Ferrari DM (2003) Crystal structure and functional analysis of Drosophila Wind, a protein-disulfide isomerase-related protein. J Biol Chem 278:44600-44607

    PubMed  CAS  Google Scholar 

  • 83. Matsuda S, Shibasaki F, Takehana K, Mori H, Nishida E, Koyasu S (2000) Two distinct action mechanisms of immunophilin-ligand complexes for the blockade of T-cell activation. EMBO Rep 1:428-434

    PubMed  CAS  Google Scholar 

  • 84. Mattaj IW (2004) Sorting out the nuclear envelope from the endoplasmic reticulum. Nat Rev Mol Cell Biol 5:65-69

    PubMed  CAS  Google Scholar 

  • 85. Matter K, Yamamoto EM, Mellman I (1994) Structural requirements and sequence motifs for polarized sorting and endocytosis of LDL and Fc receptors in MDCK cells. J Cell Biol 126:991-1004

    PubMed  CAS  Google Scholar 

  • 86. Meacham GC, Patterson C, Zhang W, Younger JM, Cyr DM (2001) The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat Cell Biol 3:100-105

    PubMed  CAS  Google Scholar 

  • 87. Medeiros-Neto G, Kim PS, Yoo SE, Vono J, Targovnik HM, Camargo R, Hossain SA, Arvan P (1996) Congenital hypothyroid goiter with deficient thyroglobulin. Identification of an endoplasmic reticulum storage disease with induction of molecular chaperones. J Clin Invest 98:2838-2844

    PubMed  CAS  Google Scholar 

  • 88. Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52:711-760

    PubMed  CAS  Google Scholar 

  • 89. Meunier L, Usherwood Y-K, Chung KT, Hendershot LM (2002) A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins. Mol Biol Cell 13:4456-4469

    PubMed  CAS  Google Scholar 

  • 90. Mezghrani A, Fassio A, Benham A, Simmen T, Braakman I, Sitia R (2001) Manipulation of oxidative protein folding and PDI redox state in mammalian cells. EMBO J 20:6288-6296

    PubMed  CAS  Google Scholar 

  • 91. Mittal V (2004) Improving the efficiency of RNA interference in mammals. Nat Rev Genet 5:355-365

    PubMed  CAS  Google Scholar 

  • 92. Molinari M, Calanca V, Galli C, Lucca P, Paganetti P (2003) Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle. Science 299:1397-1400

    PubMed  CAS  Google Scholar 

  • 93. Molinari M, Helenius A (1999) Glycoproteins form mixed disulphides with oxidoreductases during folding in living cells. Nature 402:90-93

    PubMed  CAS  Google Scholar 

  • 94. Molinari M, Helenius A (2000) Chaperone selection during glycoprotein translocation into the endoplasmic reticulum. Science 288:331-333

    PubMed  CAS  Google Scholar 

  • 95. Molteni Sn, Fassio A, Ciriolo Mr, Filomeni G, Pasqualetto E, Fagioli C, Sitia R (2004) Glutathione limits Ero1-dependent oxidation in the endoplasmic reticulum. J Biol Chem 279:32667-32673

    PubMed  CAS  Google Scholar 

  • 96. Munro S, Pelham H (1986) An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell 46:291-300

    PubMed  CAS  Google Scholar 

  • 97. Nelson WJ, Yeaman C (2001) Protein trafficking in the exocytic pathway of polarized epithelial cells. Trends Cell Biol 1:483-486

    Google Scholar 

  • 98. Norgaard P, Westphal V, Tachibana C, Alsoe L, Holst B, Winther JR (2001) Functional differences in yeast protein disulfide isomerases. J Cell Biol 152:553-562

    PubMed  CAS  Google Scholar 

  • 99. Oda Y, Hosokawa N, Wada I, Nagata K (2003) EDEM as an acceptor of terminally misfolded glycoproteins released from calnexin. Science 299:1394-1397

    PubMed  CAS  Google Scholar 

  • 100. Okamoto K, Moriishi K, Miyamura T, Matsuura Y (2004) Intramembrane proteolysis and endoplasmic reticulum retention of Hepatitis C virus core protein. J Virol 78:6370-6380

    PubMed  CAS  Google Scholar 

  • 101. Oliver JD, Van Der Wal FJ, Bulleid NJ, High S (1997) Interaction of the thiol-dependent reductase ERp57 with nascent glycoproteins. Science 275:86-88

    PubMed  CAS  Google Scholar 

  • 102. Ostergaard H, Henriksen A, Hansen FG, Winther JR (2001) Shedding light on disulfide bond formation: engineering a redox switch in green fluorescent protein. EMBO J 20:5853-5862

    PubMed  CAS  Google Scholar 

  • 103. Ou WJ, Cameron PH, Thomas DY, Bergeron JJ (1993) Association of folding intermediates of glycoproteins with calnexin during protein maturation. Nature 364:771-776

    PubMed  CAS  Google Scholar 

  • 104. Pagani M, Fabbri M, Benedetti C, Fassio A, Pilati S, Bulleid NJ, Cabibbo A, Sitia R (2000) Endoplasmic reticulum oxidoreductin 1-lbeta (ERO1-Lbeta), a human gene induced in the course of the unfolded protein response. J Biol Chem 275:23685-23692

    PubMed  CAS  Google Scholar 

  • 105. Parlati F, Dominguez M, Bergeron JJM, Thomas DY (1995) Saccharomyces cerevisiae CNE1 encodes an endoplasmic reticulum (ER) membrane protein with sequence similarity to calnexin and calreticulin and functions as a constituent of the ER quality control apparatus. J Biol Chem 270:244-253

    PubMed  CAS  Google Scholar 

  • 106. Peters T Jr, Davidson LK (1982) The biosynthesis of rat serum albumin. In vivo studies on the formation of the disulfide bonds. J Biol Chem 257:8847-8853

    PubMed  CAS  Google Scholar 

  • 107. Plemper RK, Bohmler S, Bordallo J, Sommer T, Wolf DH (1997) Mutant analysis links the translocon and BiP to retrograde protein transport for ER degradation. Nature 388:891-895

    PubMed  CAS  Google Scholar 

  • 108. Pollard MG, Travers KJ, Weissman JS (1998) Ero1p: a novel and ubiquitous protein with an essential role in oxidative protein folding in the endoplasmic reticulum. Mol Cell 1:171-182

    PubMed  CAS  Google Scholar 

  • 109. Pollock S, Kozlov G, Pelletier MF, Trempe JF, Jansen G, Sitnikov D, Bergeron JJ, Gehring K, Ekiel I, Thomas DY (2004) Specific interaction of ERp57 and calnexin determined by NMR spectroscopy and an ER two-hybrid system. EMBO J 23:1020-1029

    PubMed  CAS  Google Scholar 

  • 110. Potter BA, Ihrke G, Bruns JR, Weixel KM, Weisz OA (2004) Specific N-Glycans direct apical delivery of transmembrane, but not soluble or glycosylphosphatidylinositol-anchored forms of endolyn in Madin-Darby canine kidney cells. Mol Biol Cell 15:1407-1416

    PubMed  CAS  Google Scholar 

  • 111. Ramos M, Lopez De Castro JA (2002) HLA-B27 and the pathogenesis of spondyloarthritis. Tissue Antigens 60:191-205

    PubMed  CAS  Google Scholar 

  • 112. Riederer MA, Hinnen A (1991) Removal of N-glycosylation sites of the yeast acid phosphatase severely affects protein folding. J Bacteriol 173:3539-3546

    PubMed  CAS  Google Scholar 

  • 113. Ritter C, Helenius A (2000) Recognition of local glycoprotein misfolding by the ER folding sensor UDP-glucose:glycoprotein glucosyltransferase. Nat Struct Biol 7:278-280

    PubMed  CAS  Google Scholar 

  • 114. Russell SJ, Ruddock LW, Salo KEH, Oliver JD, Roebuck QP, Llewellyn DH, Roderick Hl, Koivunen P, Myllyharju J, High S (2004) The primary substrate binding site in the b' domain of ERp57 is adapted for endoplasmic reticulum lectin association. J Biol Chem 279:18861-18869

    PubMed  CAS  Google Scholar 

  • 115. Saito Y, Ihara Y, Leach MR, Cohen-Doyle MF, Williams DB (1999) Calreticulin functions in vitro as a molecular chaperone for both glycosylated and non-glycosylated proteins. EMBO J 18:6718-6729

    PubMed  CAS  Google Scholar 

  • 116. Saksena S, Shao Y, Braunagel SC, Summers MD, Johnson AE (2004) Cotranslational integration and initial sorting at the endoplasmic reticulum translocon of proteins destined for the inner nuclear membrane. Proc Natl Acad Sci USA 101:12537-12542

    PubMed  CAS  Google Scholar 

  • 117. Sargsyan E, Baryshev M, Szekely L, Sharipo A, Mkrtchian S (2002) Identification of ERp29, an endoplasmic reticulum lumenal protein, as a new member of the thyroglobulin folding complex. J Biol Chem 277:17009-17015

    PubMed  CAS  Google Scholar 

  • 118. Scheiffele P, Peranen J, Simons K (1995) N-glycans as apical sorting signals in epithelial cells. Nature 378:96-98

    PubMed  CAS  Google Scholar 

  • 119. Schrag JD, Bergeron JJM, Li Y, Borisova S, Hahn M, Thomas DY, Cygler M (2001) The structure of calnexin, an ER chaperone involved in quality control of protein folding. Mol Cell 8:633-644

    PubMed  CAS  Google Scholar 

  • 120. Schymkowitz JWH, Rousseau F, Serrano L (2002) Surfing on protein folding energy landscapes. Proc Natl Acad Sci USA 99:15846-15848

    PubMed  CAS  Google Scholar 

  • 121. Sen J, Goltz J, Konsolaki M, Schupbach T, Stein D (2000) Windbeutel is required for function and correct subcellular localization of the Drosophila patterning protein Pipe. Development 127:5541-5550

    PubMed  CAS  Google Scholar 

  • 122. Sevier CS, Cuozzo JW, Vala A, Aslund F, Kaiser CA (2001) A flavoprotein oxidase defines a new endoplasmic reticulum pathway for biosynthetic disulphide bond formation. Nat Cell Biol 3:874-882

    PubMed  CAS  Google Scholar 

  • 123. Sharma M, Pampinella F, Nemes C, Benharouga M, So J, Du K, Bache Kg, Papsin B, Zerangue N, Stenmark H, Lukacs Gl (2004) Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes. J Cell Biol 164:923-933

    PubMed  CAS  Google Scholar 

  • 124. Shelness G, Lin L, Nicchitta C (1993) Membrane topology and biogenesis of eukaryotic signal peptidase. J Biol Chem 268:5201-5208

    PubMed  CAS  Google Scholar 

  • 125. Silberstein S, Schlenstedt G, Silver Pa, Gilmore R (1998) A role for the DnaJ homologue Scj1p in protein folding in the yeast endoplasmic reticulum. J Cell Biol 143:921-933

    PubMed  CAS  Google Scholar 

  • 126. Silvennoinen L, Myllyharju J, Ruoppolo M, Orru S, Caterino M, Kivirikko KI, Koivunen P (2004) Identification and characterization of structural domains of human ERp57: association with calreticulin requires several domains. J Biol Chem 279:13607-13615

    PubMed  CAS  Google Scholar 

  • 127. Smith M, Koch G (1989) Multiple zones in the sequence of calreticulin (CRP55, calregulin, HACBP), a major calcium binding ER/SR protein. EMBO J 8:3581-3586

    PubMed  CAS  Google Scholar 

  • 128. Solovyov A, Gilbert HF (2004) Zinc-dependent dimerization of the folding catalyst, protein disulfide isomerase. Protein Sci 13:1902-1907

    PubMed  CAS  Google Scholar 

  • 129. Solovyov A, Xiao R, Gilbert Hf (2004) Sulfhydryl oxidation, not disulfide isomerization, is the principal function of protein disulfide isomerase in yeast Saccharomyces cerevisiae. J Biol Chem 279:34095-34100

    PubMed  CAS  Google Scholar 

  • 130. Spooner RA, Watson PD, Marsden CJ, Smith DC, Moore KA, Cook JP, Lord JM, Roberts LM (2004) Protein disulphide isomerase reduces ricin to its A and B chains in the endoplasmic reticulum. Biochem J 383:285-293

    PubMed  CAS  Google Scholar 

  • 131. Stillemark P, Boren J, Andersson M, Larsson T, Rustaeus S, Karlsson K-A, Olofsson S-O (2000) The assembly and secretion of Apolipoprotein B-48-containing very low density lipoproteins in McA-RH7777 cells. J Biol Chem 275:10506-10513

    PubMed  CAS  Google Scholar 

  • 132. Strickland E, Qu B-H, Millen L, Thomas PJ (1997) The molecular chaperone Hsc70 assists the in vitro folding of the N-terminal nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator. J Biol Chem 272:25421-25424

    PubMed  CAS  Google Scholar 

  • 133. Suh J-K, Poulsen LL, Ziegler DM, Robertus JD (1999) Yeast flavin-containing monooxygenase generates oxidizing equivalents that control protein folding in the endoplasmic reticulum. Proc Natl Acad Sci USA 96:2687-2691

    PubMed  CAS  Google Scholar 

  • 134. Sullivan DC, Huminiecki L, Moore JW, Boyle JJ, Poulsom R, Creamer D, Barker J, Bicknell R (2003) EndoPDI, a novel protein-disulfide isomerase-like protein that is preferentially expressed in endothelial cells acts as a stress survival factor. J Biol Chem 278:47079-47088

    PubMed  CAS  Google Scholar 

  • 135. Swanton E, High S, Woodman P (2003) Role of calnexin in the glycan-independent quality control of proteolipid protein. EMBO J 22:2948-2958

    PubMed  CAS  Google Scholar 

  • 136. Trombetta ES, Helenius A (2000) Conformational requirements for glycoprotein reglucosylation in the endoplasmic reticulum. J Cell Biol 148:1123-1129

    PubMed  CAS  Google Scholar 

  • 137. Tsai B, Rodighiero C, Lencer WI, Rapoport TA (2001) Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin. Cell 104:937-948

    PubMed  CAS  Google Scholar 

  • 138. Tu BP, Ho-Schleyer SC, Travers KJ, Weissman JS (2000) Biochemical basis of oxidative protein folding in the endoplasmic reticulum. Science 290:1571-1574

    PubMed  CAS  Google Scholar 

  • 139. Tu BP, Weissman JS (2004) Oxidative protein folding in eukaryotes: mechanisms and consequneces. J Cell Biol 164:341-346

    PubMed  CAS  Google Scholar 

  • 140. Vanhove M, Usherwood YK, Hendershot LM (2001) Unassembled Ig heavy chains do not cycle from BiP in vivo but require light chains to trigger their release. Immunity 15:105-114

    PubMed  CAS  Google Scholar 

  • 141. van Lith M, Hartigan N, Hatch J, Benham AM (2005) PDILT, a divergent testis-specific protein disulfide isomerase with a non-classical SXXC motif that engages in disulfide-dependent interactions in the endoplasmic reticulum. J Biol Chem 280:1376-1383

    Google Scholar 

  • 142. Vashist S, Ng DTW (2004) Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control. J Cell Biol 165:41-52

    PubMed  CAS  Google Scholar 

  • 143. Voisset C, Dubuisson J (2004) Functional hepatitis C virus envelope glycoproteins. Biol Cell 96:413-420

    PubMed  CAS  Google Scholar 

  • 144. Wang Q, Chang A (1999) Eps1, a novel PDI-related protein involved in ER quality control in yeast. EMBO J 18:5972-5982

    PubMed  CAS  Google Scholar 

  • 145. Watanabe R, Riezman H (2004) Differential ER exit in yeast and mammalian cells. Curr Opin Cell Biol 16:350-355

    PubMed  CAS  Google Scholar 

  • 146. Wearsch PA, Jakob CA, Vallin A, Dwek RA, Rudd PM, Cresswell P (2004) Major histocompatibility complex class I molecules expressed with monoglucosylated N-linked glycans bind calreticulin independently of their assembly status. J Biol Chem 279:25112-25121

    PubMed  CAS  Google Scholar 

  • 147. Wehrens XHT, Lehnart SE, Reiken SR, Deng S-X, Vest JA, Cervantes D, Coromilas J, Landry DW, Marks AR (2004) Protection from cardiac arrhythmia through ryanodine receptor-stabilizing protein calstabin2. Science 304:292-296

    PubMed  CAS  Google Scholar 

  • 148. Weihofen A, Binns K, Lemberg MK, Ashman K, Martoglio B (2002) Identification of signal peptide peptidase, a presenilin-type aspartic protease. Science 296:2215-2218

    PubMed  CAS  Google Scholar 

  • 149. Weihofen A, Martoglio B (2003) Intramembrane-cleaving proteases: controlled liberation of proteins and bioactive peptides. Trends Cell Biol 13:71-78

    PubMed  CAS  Google Scholar 

  • 150. Wigley WC, Stidham RD, Smith NM, Hunt JF, Thomas PJ (2001) Protein solubility and folding monitored in vivo by structural complementation of a genetic marker protein. Nat Biotechnol 19:131-136

    PubMed  CAS  Google Scholar 

  • 151. Wilson IA, Skehel JJ, Wiley DC (1981) Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 289:366-373

    PubMed  CAS  Google Scholar 

  • 152. Woolhead CA, Mccormick PJ, Johnson AE (2004) Nascent membrane and secretory proteins differ in FRET-detected folding far inside the ribosome and in their exposure to ribosomal proteins. Cell 116:725-736

    PubMed  CAS  Google Scholar 

  • 153. Xia W, Wolfe MS (2003) Intramembrane proteolysis by presenilin and presenilin-like proteases. J Cell Sci 116:2839-2844

    PubMed  CAS  Google Scholar 

  • 154. Zeigler DM (2002) An overview of the mechanism, substrate specificities, and structure of FMOs. Drug Metab Rev 34:503-511

    Google Scholar 

  • 155. Zhang J, Herscovitz H (2003) Nascent lipidated apolipoprotein B is transported to the golgi as an incompletely folded intermediate as probed by its association with network of endoplasmic reticulum molecular chaperones, GRP94, ERp72, BiP, calreticulin, and cyclophilin B. J Biol Chem 278:7459-7468

    PubMed  CAS  Google Scholar 

  • 156. Zhang X, Wang Y, Li H, Zhang W, Wu D, Mi H (2004) The mouse FKBP23 binds to BiP in ER and the binding of C-terminal domain is interrelated with Ca2+ concentration. FEBS Lett 559:57-60

    PubMed  CAS  Google Scholar 

  • 157. Ziegler DM (1985) Role of reversible oxidation-reduction of enzyme thiols-disulfides in metabolic regulation. Annu Rev Biochem 54:305-329

    PubMed  CAS  Google Scholar 

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  1. Department of Biological Sciences, University of Durham, South Road, Durham, DH1 3LE, England

    Sanjika Dias-Gunasekara & Adam M. Benham

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  1. Sanjika Dias-Gunasekara
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Dias-Gunasekara, S., Benham, A.M. Folding of newly synthesised proteins in the endoplasmic reticulum. In: Braakman, I. (eds) Chaperones. Topics in Current Genetics, vol 16. Springer, Berlin, Heidelberg. https://doi.org/10.1007/4735_110

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