Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

N-glycan structure dictates extension of protein folding or onset of disposal


The endoplasmic reticulum (ER) is the site of folding for proteins that are resident in the ER or that are destined for the Golgi, endosomes, lysosomes, the plasma membrane, or secretion. Cotranslational addition of preassembled glucose3-mannose9-N-acetylglucosamine2 core oligosaccharides (N-glycosylation) is a common event for polypeptides synthesized in this compartment. Protein-bound oligosaccharides are exposed to several ER glycanases that sequentially remove terminal glucose or mannose residues. Their activity must be tightly regulated because the N-glycan composition determines whether the associated protein is subjected to folding attempts in the ER lumen or whether it is retrotranslocated into the cytosol and degraded.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: The fate of newly synthesized glycoproteins in the ER lumen.
Figure 2: N-glycan processing in the mammalian and yeast ER.
Figure 3: The members of the GH47 family.
Figure 4: Schematic view of degradation kinetics for a model glycoprotein.


  1. 1

    Ellgaard, L., Molinari, M. & Helenius, A. Setting the standards: quality control in the secretory pathway. Science 286, 1882–1888 (1999).

    CAS  PubMed  Google Scholar 

  2. 2

    Meusser, B., Hirsch, C., Jarosch, E. & Sommer, T. ERAD: the long road to destruction. Nat. Cell Biol. 7, 766–772 (2005).

    CAS  PubMed  Google Scholar 

  3. 3

    Romisch, K. Endoplasmic reticulum-associated degradation. Annu. Rev. Cell Dev. Biol. 21, 435–456 (2005).

    CAS  PubMed  Google Scholar 

  4. 4

    McCracken, A.A. & Brodsky, J.L. Evolving questions and paradigm shifts in endoplasmic-reticulum-associated degradation (ERAD). Bioessays 25, 868–877 (2003).

    CAS  PubMed  Google Scholar 

  5. 5

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

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Hebert, D.N., Garman, S.C. & Molinari, M. The glycan code of the endoplasmic reticulum: asparagine-linked carbohydrates as protein maturation and quality-control tags. Trends Cell Biol. 15, 364–370 (2005).

    CAS  PubMed  Google Scholar 

  7. 7

    Molinari, M. & Helenius, A. Chaperone selection during glycoprotein translocation into the endoplasmic reticulum. Science 288, 331–333 (2000).

    CAS  PubMed  Google Scholar 

  8. 8

    Soldà, T., Garbi, N., Hammerling, G.J. & Molinari, M. Consequences of ERp57 deletion on oxidative folding of obligate and facultative clients of the calnexin cycle. J. Biol. Chem. 281, 6219–6226 (2006).

    PubMed  Google Scholar 

  9. 9

    Zapun, A. et al. Enhanced catalysis of ribonuclease B folding by the interaction of calnexin or calreticulin with ERp57. J. Biol. Chem. 273, 6009–6012 (1998).

    CAS  PubMed  Google Scholar 

  10. 10

    Oliver, J.D., van der Wal, F.J., Bulleid, N.J. & High, S. Interaction of the thiol-dependent reductase ERp57 with nascent glycoproteins. Science 275, 86–88 (1997).

    CAS  PubMed  Google Scholar 

  11. 11

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

    CAS  PubMed  Google Scholar 

  12. 12

    Jessop, C.E. et al. ERp57 is essential for efficient folding of glycoproteins sharing common structural domains. EMBO J. 26, 28–40 (2007).

    CAS  PubMed  Google Scholar 

  13. 13

    Maattanen, P., Kozlov, G., Gehring, K. & Thomas, D.Y. ERp57 and PDI: multifunctional protein disulfide isomerases with similar domain architectures but differing substrate–partner associations. Biochem. Cell Biol. 84, 881–889 (2006).

    CAS  PubMed  Google Scholar 

  14. 14

    Gurkan, C., Stagg, S.M., Lapointe, P. & Balch, W.E. The COPII cage: unifying principles of vesicle coat assembly. Nat. Rev. Mol. Cell Biol. 7, 727–738 (2006).

    PubMed  Google Scholar 

  15. 15

    Molinari, M., Galli, C., Vanoni, O., Arnold, S.M. & Kaufman, R.J. Persistent glycoprotein misfolding activates the glucosidase II/UGT1-driven calnexin cycle to delay aggregation and loss of folding competence. Mol. Cell 20, 503–512 (2005).

    CAS  PubMed  Google Scholar 

  16. 16

    Kopito, R.R. Biosynthesis and degradation of CFTR. Physiol. Rev. 79, S167–S173 (1999).

    CAS  PubMed  Google Scholar 

  17. 17

    Kopito, R.R. & Ron, D. Conformational disease. Nat. Cell Biol. 2, E207–E209 (2000).

    CAS  PubMed  Google Scholar 

  18. 18

    Molinari, M. & Sitia, R. The secretory capacity of a cell depends on the efficiency of endoplasmic reticulum-associated degradation. Curr. Top. Microbiol. Immunol. 300, 1–15 (2005).

    CAS  PubMed  Google Scholar 

  19. 19

    Eriksson, K.K. et al. EDEM contributes to maintenance of protein folding efficiency and secretory capacity. J. Biol. Chem. 279, 44600–44605 (2004).

    CAS  PubMed  Google Scholar 

  20. 20

    Ruddock, L.W. & Molinari, M. N-glycan processing in ER quality control. J. Cell Sci. 119, 4373–4380 (2006).

    CAS  Google Scholar 

  21. 21

    Yoshida, Y., Murakami, A., Iwai, K. & Tanaka, K. A neural-specific F-box protein FBS1 functions as a chaperone suppressing glycoprotein aggregation. J. Biol. Chem. 282, 7137–7144 (2007).

    CAS  PubMed  Google Scholar 

  22. 22

    Yoshida, Y. et al. E3 ubiquitin ligase that recognizes sugar chains. Nature 418, 438–442 (2002).

    CAS  PubMed  Google Scholar 

  23. 23

    Hirsch, C., Blom, D. & Ploegh, H.L. A role for N-glycanase in the cytosolic turnover of glycoproteins. EMBO J. 22, 1036–1046 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Caramelo, J.J., Castro, O.A., de Prat-Gay, G. & Parodi, A.J. The endoplasmic reticulum glucosyltransferase recognizes nearly native glycoprotein folding intermediates. J. Biol. Chem. 279, 46280–46285 (2004).

    CAS  PubMed  Google Scholar 

  25. 25

    Ritter, C., Quirin, K., Kowarik, M. & Helenius, A. Minor folding defects trigger local modification of glycoproteins by the ER folding sensor GT. EMBO J. 24, 1730–1738 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Molinari, M., Galli, C., Piccaluga, V., Pieren, M. & Paganetti, P. Sequential assistance of molecular chaperones and transient formation of covalent complexes during protein degradation from the ER. J. Cell Biol. 158, 247–257 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Cabral, C.M., Liu, Y., Moremen, K.W. & Sifers, R.N. Organizational diversity among distinct glycoprotein endoplasmic reticulum-associated degradation programs. Mol. Biol. Cell 13, 2639–2650 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Svedine, S., Wang, T., Halaban, R. & Hebert, D.N. Carbohydrates act as sorting determinants in ER-associated degradation of tyrosinase. J. Cell Sci. 117, 2937–2949 (2004).

    CAS  PubMed  Google Scholar 

  29. 29

    Hendershot, L.M. The ER function BiP is a master regulator of ER function. Mt. Sinai J. Med. 71, 289–297 (2004).

    PubMed  Google Scholar 

  30. 30

    Taylor, S.C., Ferguson, A.D., Bergeron, J.J. & Thomas, D.Y. The ER protein folding sensor UDP-glucose glycoprotein-glucosyltransferase modifies substrates distant to local changes in glycoprotein conformation. Nat. Struct. Mol. Biol. 11, 128–134 (2004).

    CAS  PubMed  Google Scholar 

  31. 31

    Moremen, K.W. in Alpha-Mannosidases in Asparagine-Linked Oligosaccharide Processing and Catabolism Vol. 2 (eds. Ernst, B., Hart, G. & Sinay, P.) 81–117 (John Wiley and Sons, Inc., New York, 2000).

    Google Scholar 

  32. 32

    Lederkremer, G.Z. & Glickman, M.H. A window of opportunity: timing protein degradation by trimming of sugars and ubiquitins. Trends Biochem. Sci. 30, 297–303 (2005).

    CAS  PubMed  Google Scholar 

  33. 33

    Sousa, M.C., Ferrero-Garcia, M.A. & Parodi, A.J. Recognition of the oligosaccharide and protein moieties of glycoproteins by the UDP-Glc:glycoprotein glucosyltransferase. Biochemistry 31, 97–105 (1992).

    CAS  PubMed  Google Scholar 

  34. 34

    Spiro, R.G., Zhu, Q., Bhoyroo, V. & Soling, H.D. Definition of the lectin-like properties of the molecular chaperone, calreticulin, and demonstration of its copurification with endomannosidase from rat liver Golgi. J. Biol. Chem. 271, 11588–11594 (1996).

    CAS  PubMed  Google Scholar 

  35. 35

    Cabral, C.M., Liu, Y. & Sifers, R.N. Dissecting glycoprotein quality control in the secretory pathway. Trends Biochem. Sci. 26, 619–624 (2001).

    CAS  PubMed  Google Scholar 

  36. 36

    Moremen, K.W. & Molinari, M. N-linked glycan recognition and processing: the molecular basis of endoplasmic reticulum quality control. Curr. Opin. Struct. Biol. 16, 592–599 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Jakob, C.A., Burda, P., Roth, J. & Aebi, M. Degradation of misfolded endoplasmic reticulum glycoproteins in Saccharomyces cerevisiae is determined by a specific oligosaccharide structure. J. Cell Biol. 142, 1223–1233 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38

    Su, K., Stoller, T., Rocco, J., Zemsky, J. & Green, R. Pre-Golgi degradation of yeast prepro-alpha-factor expressed in a mammalian cell. Influence of cell type-specific oligosaccharide processing on intracellular fate. J. Biol. Chem. 268, 14301–14309 (1993).

    CAS  PubMed  Google Scholar 

  39. 39

    Foulquier, F. et al. The unfolded protein response in a dolichyl phosphate mannose-deficient Chinese hamster ovary cell line points out the key role of a demannosylation step in the quality-control mechanism of N-glycoproteins. Biochem. J. 362, 491–498 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    Kitzmuller, C. et al. Processing of N-linked glycans during endoplasmic-reticulum-associated degradation of a short-lived variant of ribophorin I. Biochem. J. 376, 687–696 (2003).

    PubMed  PubMed Central  Google Scholar 

  41. 41

    Foulquier, F. et al. Endoplasmic reticulum-associated degradation of glycoproteins bearing Man5GlcNAc2 and Man9GlcNAc2 species in the MI8–5 CHO cell line. Eur. J. Biochem. 271, 398–404 (2004).

    CAS  PubMed  Google Scholar 

  42. 42

    Frenkel, Z., Gregory, W., Kornfeld, S. & Lederkremer, G.Z. Endoplasmic reticulum-associated degradation of mammalian glycoproteins involves sugar chain trimming to Man6–5GlcNAc2. J. Biol. Chem. 278, 34119–34124 (2003).

    CAS  PubMed  Google Scholar 

  43. 43

    Hosokawa, N. et al. Enhancement of endoplasmic reticulum (ER) degradation of misfolded Null Hong Kong α1-antitrypsin by human ER mannosidase I. J. Biol. Chem. 278, 26287–26294 (2003).

    CAS  PubMed  Google Scholar 

  44. 44

    Cacan, R. et al. Different fates of the oligosaccharide moieties of lipid intermediates. Glycobiology 2, 127–136 (1992).

    CAS  PubMed  Google Scholar 

  45. 45

    Ermonval, M., Kitzmuller, C., Mir, A.M., Cacan, R. & Ivessa, N.E. N-glycan structure of a short-lived variant of ribophorin I expressed in the MadIA214 glycosylation-defective cell line reveals the role of a mannosidase that is not ER mannosidase I in the process of glycoprotein degradation. Glycobiology 11, 565–576 (2001).

    CAS  PubMed  Google Scholar 

  46. 46

    Olivari, S. et al. EDEM1 regulates ER-associated degradation by accelerating de-mannosylation of folding-defective polypeptides and by inhibiting their covalent aggregation. Biochem. Biophys. Res. Commun. 349, 1278–1284 (2006).

    CAS  PubMed  Google Scholar 

  47. 47

    Karaveg, K. et al. Mechanism of class 1 (glycosylhydrolase family 47) α-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control. J. Biol. Chem. 280, 16197–16207 (2005).

    CAS  Google Scholar 

  48. 48

    Hirao, K. et al. EDEM3, a soluble EDEM homolog, enhances glycoprotein ERAD and mannose trimming. J. Biol. Chem. 281, 9650–9658 (2006).

    CAS  PubMed  Google Scholar 

  49. 49

    Hosokawa, N., Wada, I., Natsuka, Y. & Nagata, K. EDEM accelerates ERAD by preventing aberrant dimer formation of misfolded α1-antitrypsin. Genes Cells 11, 465–476 (2006).

    CAS  PubMed  Google Scholar 

  50. 50

    Fernandez, F.S., Trombetta, S.E., Hellman, U. & Parodi, A.J. Purification to homogeneity of UDP-glucose:glycoprotein glucosyltransferase from Schizosaccharomyces pombe and apparent absence of the enzyme fro Saccharomyces cerevisiae. J. Biol. Chem. 269, 30701–30706 (1994).

    CAS  PubMed  Google Scholar 

  51. 51

    Lippincott Schwartz, J., Bonifacino, J.S., Yuan, L.C. & Klausner, R.D. Degradation from the endoplasmic reticulum: disposing of newly synthesized proteins. Cell 54, 209–220 (1988).

    CAS  PubMed  Google Scholar 

  52. 52

    Le, A., Graham, K.S. & Sifers, R.N. Intracellular degradation of the transport-impaired human PiZ α1- antitrypsin variant. Biochemical mapping of the degradative event among compartments of the secretory pathway. J. Biol. Chem. 265, 14001–14007 (1990).

    CAS  PubMed  Google Scholar 

  53. 53

    Amara, J.F., Lederkremer, G. & Lodish, H.F. Intracellular degradation of unassembled asialoglycoprotein receptor subunits: a pre-Golgi, nonlysosomal endoproteolytic cleavage. J. Cell Biol. 109, 3315–3324 (1989).

    CAS  PubMed  Google Scholar 

  54. 54

    Fagioli, C. & Sitia, R. Glycoprotein quality control in the endoplasmic reticulum. Mannose trimming by endoplasmic reticulum mannosidase I times the proteasomal degradation of unassembled immunoglobulin subunits. J. Biol. Chem. 276, 12885–12892 (2001).

    CAS  PubMed  Google Scholar 

  55. 55

    Mancini, R., Aebi, M. & Helenius, A. Multiple endoplasmic reticulum-associated pathways degrade mutant yeast carboxypeptidase Y in mammalian cells. J. Biol. Chem. 278, 46895–46905 (2003).

    CAS  PubMed  Google Scholar 

  56. 56

    de Virgilio, M. et al. Degradation of a short-lived glycoprotein from the lumen of the endoplasmic reticulum: the role of N-linked glycans and the unfolded protein response. Mol. Biol. Cell 10, 4059–4073 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57

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

    CAS  PubMed  Google Scholar 

  58. 58

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

    CAS  PubMed  Google Scholar 

  59. 59

    Olivari, S., Galli, C., Alanen, H., Ruddock, L. & Molinari, M. A novel stress-induced EDEM variant regulating endoplasmic reticulum-associated glycoprotein degradation. J. Biol. Chem. 280, 2424–2428 (2005).

    CAS  PubMed  Google Scholar 

  60. 60

    Yoshida, H. et al. A time-dependent phase shift in the mammalian unfolded protein response. Dev. Cell 4, 265–271 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Mast, S.W. et al. Human EDEM2, a novel homolog of family 47 glycosidases, is involved in ER-associated degradation of glycoproteins. Glycobiology 15, 421–436 (2005).

    CAS  PubMed  Google Scholar 

  62. 62

    Wu, Y., Swulius, M.T., Moremen, K.W. & Sifers, R.N. Elucidation of the molecular logic by which misfolded α1-antitrypsin is preferentially selected for degradation. Proc. Natl. Acad. Sci. USA 100, 8229–8234 (2003).

    CAS  PubMed  Google Scholar 

  63. 63

    Oyadomari, S. et al. Cotranslocational degradation protects the stressed endoplasmic reticulum from protein overload. Cell 126, 727–739 (2006).

    CAS  PubMed  Google Scholar 

  64. 64

    Wang, J. & White, A.L. Role of calnexin, calreticulin, and endoplasmic reticulum mannosidase I in apolipoprotein(a) intracellular targeting. Biochemistry 39, 8993–9000 (2000).

    CAS  PubMed  Google Scholar 

  65. 65

    White, A.L., Guerra, B., Wang, J. & Lanford, R.E. Presecretory degradation of apolipoprotein [a] is mediated by the proteasome pathway. J. Lipid Res. 40, 275–286 (1999).

    CAS  PubMed  Google Scholar 

  66. 66

    Okiyoneda, T. et al. Delta F508 CFTR pool in the endoplasmic reticulum is increased by calnexin overexpression. Mol. Biol. Cell 15, 563–574 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Gong, Q., Keeney, D.R., Molinari, M. & Zhou, Z. Degradation of trafficking-defective long QT syndrome type II mutant channels by the ubiquitin-proteasome pathway. J. Biol. Chem. 280, 19419–19425 (2005).

    CAS  PubMed  Google Scholar 

  68. 68

    Pearse, B.R. & Hebert, D.N. Cotranslocational degradation: utilitarianism in the ER stress response. Mol. Cell 23, 773–775 (2006).

    CAS  PubMed  Google Scholar 

  69. 69

    Kang, S.W. et al. Substrate-specific translocational attenuation during ER stress defines a pre-emptive quality control pathway. Cell 127, 999–1013 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70

    Matlack, K.E., Misselwitz, B., Plath, K. & Rapoport, T.A. BiP acts as a molecular ratchet during posttranslational transport of prepro-alpha factor across the ER membrane. Cell 97, 553–564 (1999).

    CAS  PubMed  Google Scholar 

  71. 71

    Schroder, M. & Kaufman, R.J. The mammalian unfolded protein response. Annu. Rev. Biochem. 74, 739–789 (2005).

    Google Scholar 

  72. 72

    Yoshida, H., Matsui, T., Yamamoto, A., Okada, T. & Mori, K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107, 881–891 (2001).

    CAS  Google Scholar 

  73. 73

    Lee, K. et al. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev. 16, 452–466 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    Hollien, J. & Weissman, J.S. Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science 313, 104–107 (2006).

    CAS  Google Scholar 

  75. 75

    Aridor, M. & Hannan, L.A. Traffic jams II: an update of diseases of intracellular transport. Traffic 3, 781–790 (2002).

    CAS  PubMed  Google Scholar 

  76. 76

    Vij, N., Fang, S. & Zeitlin, P.L. Selective inhibition of endoplasmic reticulum-associated degradation rescues DeltaF508-cystic fibrosis transmembrane regulator and suppresses interleukin-8 levels: therapeutic implications. J. Biol. Chem. 281, 17369–17378 (2006).

    CAS  PubMed  Google Scholar 

  77. 77

    Bernier, V., Bichet, D.G. & Bouvier, M. Pharmacological chaperone action on G-protein-coupled receptors. Curr. Opin. Pharmacol. 4, 528–533 (2004).

    CAS  PubMed  Google Scholar 

  78. 78

    Dyson, H.J., Wright, P.E. & Scheraga, H.A. The role of hydrophobic interactions in initiation and propagation of protein folding. Proc. Natl. Acad. Sci. USA 103, 13057–13061 (2006).

    CAS  PubMed  Google Scholar 

  79. 79

    Kubota, K. et al. Suppressive effects of 4-phenylbutyrate on the aggregation of Pael receptors and endoplasmic reticulum stress. J. Neurochem. 97, 1259–1268 (2006).

    CAS  PubMed  Google Scholar 

  80. 80

    Zeitlin, P.L. et al. Evidence of CFTR function in cystic fibrosis after systemic administration of 4-phenylbutyrate. Mol. Ther. 6, 119–126 (2002).

    CAS  PubMed  Google Scholar 

  81. 81

    Ozcan, U. et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313, 1137–1140 (2006).

    PubMed  PubMed Central  Google Scholar 

  82. 82

    Burrows, J.A., Willis, L.K. & Perlmutter, D.H. Chemical chaperones mediate increased secretion of mutant α1-antitrypsin (α1-AT) Z: a potential pharmacological strategy for prevention of liver injury and emphysema in α1-AT deficiency. Proc. Natl. Acad. Sci. USA 97, 1796–1801 (2000).

    CAS  PubMed  Google Scholar 

  83. 83

    Teckman, J.H. Lack of effect of oral 4-phenylbutyrate on serum α-1-antitrypsin in patients with α-1-antitrypsin deficiency: a preliminary study. J. Pediatr. Gastroenterol. Nutr. 39, 34–37 (2004).

    CAS  PubMed  Google Scholar 

  84. 84

    Lieberman, R.L. et al. Structure of acid β-glucosidase with pharmacological chaperone provides insight into Gaucher disease. Nat. Chem. Biol. 3, 101–107 (2007).

    CAS  PubMed  Google Scholar 

  85. 85

    Brooks, D.A. Getting into the fold. Nat. Chem. Biol. 3, 84–85 (2007).

    CAS  PubMed  Google Scholar 

  86. 86

    Bernier, V., Lagace, M., Bichet, D.G. & Bouvier, M. Pharmacological chaperones: potential treatment for conformational diseases. Trends Endocrinol. Metab. 15, 222–228 (2004).

    CAS  PubMed  Google Scholar 

  87. 87

    Morello, J.P., Petaja-Repo, U.E., Bichet, D.G. & Bouvier, M. Pharmacological chaperones: a new twist on receptor folding. Trends Pharmacol. Sci. 21, 466–469 (2000).

    CAS  PubMed  Google Scholar 

  88. 88

    Loo, T.W., Bartlett, M.C. & Clarke, D.M. Rescue of folding defects in ABC transporters using pharmacological chaperones. J. Bioenerg. Biomembr. 37, 501–507 (2005).

    CAS  PubMed  Google Scholar 

  89. 89

    Cohen, F.E. & Kelly, J.W. Therapeutic approaches to protein-misfolding diseases. Nature 426, 905–909 (2003).

    CAS  PubMed  Google Scholar 

  90. 90

    Ulloa-Aguirre, A., Janovick, J.A., Brothers, S.P. & Conn, P.M. Pharmacologic rescue of conformationally-defective proteins: implications for the treatment of human disease. Traffic 5, 821–837 (2004).

    CAS  PubMed  Google Scholar 

Download references


M.M. is supported by grants from the Foundation for Research on Neurodegenerative Diseases, Swiss National Center of Competence in Research on Neural Plasticity and Repair, Swiss National Science Foundation, Synapsis Foundation, Bangerter-Rhyner Foundation and Aetas Foundation.

Author information



Corresponding author

Correspondence to Maurizio Molinari.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Molinari, M. N-glycan structure dictates extension of protein folding or onset of disposal. Nat Chem Biol 3, 313–320 (2007).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing