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.
Keywords
- Endoplasmic Reticulum
- Major Histocompatibility Complex Class
- Protein Disulfide Isomerase
- Disulfide Bond Formation
- Endoplasmic Reticulum Chaperone
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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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
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
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
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
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
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
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
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
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
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
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
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
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
14. Bergman LW, Kuehl WM (1979) Formation of an intrachain disulfide bond on nascent immunoglobulin light chains. J Biol Chem 254:8869-8876
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
16. Bogdanov M, Dowhan W (1999) Lipid-assisted Protein Folding. J Biol Chem 274:36827-36830
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
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
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
20. Bulleid NJ, Freedman RB (1988) Defective co-translational formation of disulphide bonds in protein disulphide-isomerase-deficient microsomes. Nature 335:649-651
21. Bullough PA, Hughson FM, Skehel JJ, Wiley DC (1994) Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 371:37-43
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
23. Cannon KS, Cresswell P (2001) Quality control of transmembrane domain assembly in the tetraspanin CD82. EMBO J 20:2443-2453
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
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
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
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
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
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
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
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
32. Darby NJ, Kemmink J, Creighton TE (1996) Identifying and characterizing a structural domain of protein disulfide isomerase. Biochemistry 35:10517-10528
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
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
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
36. Ellgaard L, Helenius A (2003) Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4:181-191
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
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
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
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
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
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
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
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
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
46. Gierasch LM (1994) Molecular chaperones. Panning for chaperone-binding peptides. Curr Biol 4:173-174
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
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
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
50. Haas IG, Wabl M (1983) Immunoglobulin heavy chain binding protein. Nature 306:387-389
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
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
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
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
55. Helenius A, Aebi M (2004) Roles of N-linked glycans in the endoplasmic reticulum. Annu Rev Biochem 73:1019-1049
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
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
58. Hwang C, Sinskey AJ, Lodish HF (1992) Oxidized redox state of glutathione in the endoplasmic reticulum. Science 257:1496-1502
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
60. Iwawaki T, Akai R, Kohno K, Miura M (2004) A transgenic mouse model for monitoring endoplasmic reticulum stress. Nat Med 10:98-102
61. Jansens A, Braakman I (2002) Coordinated non-vectorial folding in a newly synthesized multidomain protein. Science 298:2401-2403
62. Johnson AE, Van Waes MA (1999) The translocon: a dynamic gateway at the ER membrane. Annu Rev Cell Dev Biol 15:799-842
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
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
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
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
67. Kim P, Kwon O, Arvan P (1996) An endoplasmic reticulum storage disease causing congenital goiter with hypothyroidism. J Cell Biol 133:517-527
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
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
70. Kopito RR (1999) Biosynthesis and degradation of CFTR. Physiol Rev 79:167-173
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
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
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
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
75. Li Y, Camacho P (2004) Ca2+-dependent redox modulation of SERCA 2b by ERp57. J Cell Biol 164:35-46
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
77. Linke K, Jakob U (2003) Not every disulfide lasts forever: disulfide bond formation as a redox switch. Antioxid Redox Signal 5:425-434
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
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
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
81. Luo L, Shoichet MS (2004) A photolabile hydrogel for guided three-dimensional cell growth and migration. Nat Mater 3:249-253
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
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
84. Mattaj IW (2004) Sorting out the nuclear envelope from the endoplasmic reticulum. Nat Rev Mol Cell Biol 5:65-69
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
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
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
88. Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52:711-760
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
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
91. Mittal V (2004) Improving the efficiency of RNA interference in mammals. Nat Rev Genet 5:355-365
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
93. Molinari M, Helenius A (1999) Glycoproteins form mixed disulphides with oxidoreductases during folding in living cells. Nature 402:90-93
94. Molinari M, Helenius A (2000) Chaperone selection during glycoprotein translocation into the endoplasmic reticulum. Science 288:331-333
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
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
97. Nelson WJ, Yeaman C (2001) Protein trafficking in the exocytic pathway of polarized epithelial cells. Trends Cell Biol 1:483-486
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
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
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
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
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
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
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
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
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
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
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
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
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
111. Ramos M, Lopez De Castro JA (2002) HLA-B27 and the pathogenesis of spondyloarthritis. Tissue Antigens 60:191-205
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
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
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
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
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
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
118. Scheiffele P, Peranen J, Simons K (1995) N-glycans as apical sorting signals in epithelial cells. Nature 378:96-98
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
120. Schymkowitz JWH, Rousseau F, Serrano L (2002) Surfing on protein folding energy landscapes. Proc Natl Acad Sci USA 99:15846-15848
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
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
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
124. Shelness G, Lin L, Nicchitta C (1993) Membrane topology and biogenesis of eukaryotic signal peptidase. J Biol Chem 268:5201-5208
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
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
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
128. Solovyov A, Gilbert HF (2004) Zinc-dependent dimerization of the folding catalyst, protein disulfide isomerase. Protein Sci 13:1902-1907
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
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
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
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
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
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
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
136. Trombetta ES, Helenius A (2000) Conformational requirements for glycoprotein reglucosylation in the endoplasmic reticulum. J Cell Biol 148:1123-1129
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
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
139. Tu BP, Weissman JS (2004) Oxidative protein folding in eukaryotes: mechanisms and consequneces. J Cell Biol 164:341-346
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
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
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
143. Voisset C, Dubuisson J (2004) Functional hepatitis C virus envelope glycoproteins. Biol Cell 96:413-420
144. Wang Q, Chang A (1999) Eps1, a novel PDI-related protein involved in ER quality control in yeast. EMBO J 18:5972-5982
145. Watanabe R, Riezman H (2004) Differential ER exit in yeast and mammalian cells. Curr Opin Cell Biol 16:350-355
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
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
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
149. Weihofen A, Martoglio B (2003) Intramembrane-cleaving proteases: controlled liberation of proteins and bioactive peptides. Trends Cell Biol 13:71-78
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
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
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
153. Xia W, Wolfe MS (2003) Intramembrane proteolysis by presenilin and presenilin-like proteases. J Cell Sci 116:2839-2844
154. Zeigler DM (2002) An overview of the mechanism, substrate specificities, and structure of FMOs. Drug Metab Rev 34:503-511
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
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
157. Ziegler DM (1985) Role of reversible oxidation-reduction of enzyme thiols-disulfides in metabolic regulation. Annu Rev Biochem 54:305-329
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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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