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Calnexin, calreticulin, and ERp57

Teammates in glycoprotein folding

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Abstract

In eukaryotic cells, the endoplasmic reticulum (ER) plays an essential role in the synthesis and maturation of a variety of important secretory and membrane proteins. For glycoproteins, the ER possesses a dedicated maturation system, which assists folding and ensures the quality of final products before ER release. Essential components of this system include the lectin chaperones calnexin (CNX) and calreticulin (CRT) and their associated co-chaperone ERp57, a glycoprotein specific thiol-disulfide oxidoreductase. The significance of this system is underscored by the fact that CNX and CRT interact with practically all glycoproteins investigated to date, and by the debilitating phenotypes revealed in knockout mice deficient in either gene. Compared to other important chaperone systems, such as the Hsp70s, Hsp90s and GroEL/GroES, the principles whereby this system works at the molecular level are relatively poorly understood. However, recent structural and biochemical data have provided important new insights into this chaperone system and present a solid basis for further mechanistic studies.

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References

  1. Kornfeld, R. and Kornfeld, S. (1985) Assembly of asparagine-linked oligosaccharides. Annu. Rev. Biochem. 54, 631–664.

    PubMed  CAS  Google Scholar 

  2. Burda, P. and Aebi, M. (1999) The dolichol pathway of N-liked glycosylation. Biochim. Biophys. Acta 1426, 239–257.

    PubMed  CAS  Google Scholar 

  3. Gavel, Y. and von Heijne, G. (1990) Sequence differences between glycosylated and non-glycosylated Asn-X-Thr/Ser acceptor sites: implications for protein engineering. Protein Eng. 3, 433–442.

    PubMed  CAS  Google Scholar 

  4. Gahmberg, C. G. and Tolvanen, M. (1996) Why mammalian cell surface proteins are glycoproteins. Trends Biochem. Sci. 21, 308–311.

    PubMed  CAS  Google Scholar 

  5. Stanley, P. and Ioffe, E. (1995) Glycosyltransferase mutants: key to new insights in glycobiology. FASEB J. 9, 1436–1444.

    PubMed  CAS  Google Scholar 

  6. Aebi, M. and Hennet, T. (2001) Congenital disorders of glycosylation: genetic model systems lead the way. Trends Cell. Biol. 11, 136–141.

    PubMed  CAS  Google Scholar 

  7. O'Connor, S. E. and Imperiali, B. (1996) Modulation of protein structure and function by asparagine-linked glycosylation. Chem. Biol. 3, 803–812.

    PubMed  Google Scholar 

  8. Dwek, R. A. (1996) Glycobiology: Toward understanding the function of sugars. Chem. Rev. 96, 683–720.

    PubMed  CAS  Google Scholar 

  9. Drickamer, K. and Taylor, M. E. (1998) Evolving views of protein glycosylation. Trends Biochem. Sci. 23, 321–324.

    PubMed  CAS  Google Scholar 

  10. Wormald, M. R. and Dwek, R. A. (1999) Glycoproteins: glycan presentation and proteinfold stability. Structure Fold. Des. 7, R155–160.

    PubMed  CAS  Google Scholar 

  11. Wormald, M. R., Petrescu, A. J., Pao, Y. L., Glithero, A., Elliott, T., and Dwek, R. A. (2002) Conformational studies of oligosaccharides and glycopeptides: complementarity of NMR, X-ray crystallography, and molecular modelling. Chem. Rev. 102, 371–386.

    PubMed  CAS  Google Scholar 

  12. Helenius, A., and Aebi, M. (2001) Intracellular functions of N-linked glycans. Science 291, 2364–2369.

    PubMed  CAS  Google Scholar 

  13. Yamashita, K., Hara-Kuge, S., and Ohkura, T. (1999) Intracellular lectins associated with N-linked glycoprotein traffic. Biochim. Biophys. Acta. 1473, 147–160.

    PubMed  CAS  Google Scholar 

  14. Hauri, H., Appenzeller, C., Kuhn, F., and Nufer, O. (2000) Lectins and traffic in the secretory pathway. EEBS Lett. 476, 32–37.

    CAS  Google Scholar 

  15. Schrag, J. D., Procopio, D. O., Cygler, M., Thomas, D. Y., and Bergeron, J. J. (2003) Lectin control of protein folding and sorting in the secretory pathway. Trends Biochem. Sci. 28, 49–57.

    PubMed  CAS  Google Scholar 

  16. Ou, W. J., Cameron, P. H., Thomas, D. Y., and Bergeron, J. J. (1993) Association of folding intermediates of glycoproteins with calnexin during protein maturation. Nature 364, 771–776.

    PubMed  CAS  Google Scholar 

  17. Jackson, M. R., Cohen-Doyle, M. F., Peterson, P. A., and Williams, D. B. (1994) Regulation of MHC class I transport by the molecular chaperone, calnexin (p88, IP90). Science 263, 384–387.

    PubMed  CAS  Google Scholar 

  18. Hebert, D. N., Foellmer, B., and Helenius, A. (1996) Calnexin and calreticulin promote folding, delay oligomerization and suppress degradation of influenza hemagglutinin in microsomes. EMBO J. 15, 2961–2968.

    PubMed  CAS  Google Scholar 

  19. Labriola, C., Cazzulo, J. J., and Parodi, A. J. (1995) Retention of glucose units added by the UDP-GLC: glycoprotein glucosyltransferase delays exit of glycoproteins from the endoplasmic reticulum. J. Cell Biol. 130, 771–779.

    PubMed  CAS  Google Scholar 

  20. Helenius, A., Trombetta, E. S., Hebert, D. N., and Simons, J. F. (1997) Calnexin, calreticulin and the folding of glycoproteins. Trends Cell Biol. 7, 193–200.

    CAS  Google Scholar 

  21. Liu, Y., Choudhury, P., Cabral, C. M., and Sifers, R. N. (1999) Oligosaccharide modification in the early secretory pathway directs the selection of a misfolded glycoprotein for degradation by the proteasome. J. Biol. Chem. 274, 5861–5867.

    PubMed  CAS  Google Scholar 

  22. Nakatsukasa, K., Nishikawa, S., Hosokawa, N., Nagata, K., and Endo, T. (2001) Mnl1p, an alpha-mannosidase-like protein in yeast Saccharomyces cerevisiae, is required for endoplasmic reticulum-associated degradation of glycoproteins. J. Biol. Chem. 276, 8635–8638.

    PubMed  CAS  Google Scholar 

  23. Hosokawa, N., Wada, I., Hasegawa, K., Yorihuzi, T., Tremblay, L. O., Herscovics, A., et al. (2001) A novel ER alpha-mannosidase-like protein accelerates ER-associated degradation. EMBO Rep. 2, 415–422.

    PubMed  CAS  Google Scholar 

  24. Jakob, C. A., Bodmer, D., Spirig, U., Battig, P., Marcil, A., Dignard, D., et al. (2001) Htm1p, a mannosidase-like protein, is involved in glycoprotein degradation in yeast. EMBO Rep. 2, 423–430.

    PubMed  CAS  Google Scholar 

  25. Braakman, I. (2001) A novel lectin in the secretory pathway. An elegant mechanism for glycoprotein elimination. EMBO Rep. 2, 666–668.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  28. Yoshida, H., Matsui, T., Hosokawa, N., Kaufman, R. J., Nagata, K., and Mori, K. (2003) A time-dependent phase shift in the mammalian unfolded protein response. Dev. Cell 4, 265–271.

    PubMed  CAS  Google Scholar 

  29. Parodi, A. J. (2000) Protein glucosylation and its role in protein folding. Annu. Rev. Biochem. 69, 69–93.

    PubMed  CAS  Google Scholar 

  30. Parodi, A. J. (2000) Role of N-oligosaccharide endoplasmic reticulum processing reactions in glycoprotein folding and degradation. Biochem. J. 348, 1–13.

    PubMed  CAS  Google Scholar 

  31. Trombetta, E. S., and Parodi, A. J. (2001) N-glycan processing and glycoprotein folding. Adv. Protein. Chem. 59, 303–344.

    PubMed  CAS  Google Scholar 

  32. Roth, J. (2002) Protein N-glycosylation along the secretory pathway: relationship to organelle topography and function, protein quality control, and cell interactions. Chem. Rev. 102, 285–303.

    PubMed  CAS  Google Scholar 

  33. Roth, J., Zuber, C., Guhl, B., Fan, J. Y., and Ziak, M. (2002) The importance of trimming reactions on asparagine-linked oligosaccharides for protein quality control. Histochem. Cell Biol. 117, 159–169.

    CAS  Google Scholar 

  34. Benham, A. M., and Braakman, I. (2000) Glycoprotein folding in the endoplasmic reticulum. Crit. Rev. Biochem. Mol. Biol. 35, 433–473.

    PubMed  CAS  Google Scholar 

  35. Fewell, S. W., Travers, K. J., Weissman, J. S., and Brodsky, J. L. (2001) The action of molecular chaperones in the early secretory pathway. Annu. Rev. Genet. 35, 149–191.

    PubMed  CAS  Google Scholar 

  36. Hurtley, S. M. and Helenius, A. (1989) Protein oligomerization in the endoplasmic reticulum. Annu. Rev. Cell Biol. 5, 277–307.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  38. Thomas, P. J., Qu, B. H., and Pedersen, P. L. (1995) Defective protein folding as a basis of human disease. Trends Biochem. Sci. 20, 456–459.

    PubMed  CAS  Google Scholar 

  39. Aridor, M. and Balch, W. E. (1999) Integration of endoplasmic reticulum signaling in health and disease. Nat. Med. 5, 745–751.

    PubMed  CAS  Google Scholar 

  40. Kopito, R. R. and Ron, D. (2000) Conformational disease. Nat. Cell Biol. 2, E207–209.

    PubMed  CAS  Google Scholar 

  41. Rutishauser, J. and Spiess, M. (2002) Endoplasmic reticulum storage diseases. Swiss Med. Wkly. 132, 211–222.

    PubMed  CAS  Google Scholar 

  42. Tsai, B., Ye, Y., and Rapoport, T. A. (2002) Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nat. Rev. Mol. Cell Biol. 3, 246–255.

    PubMed  CAS  Google Scholar 

  43. Ma, Y. and Hendershot, L. M. (2001) The unfolding tale of the unfolded protein response. Cell 107, 827–830.

    PubMed  CAS  Google Scholar 

  44. Casagrande, R., Stern, P., Diehn, M., Shamu, C., Osario, M., Zuniga, M., et al. (2000) Degradation of proteins from the ER of S. cerevisiae requires an intact unforlded protein response pathway. Mol. Cell 5, 729–735.

    PubMed  CAS  Google Scholar 

  45. Travers, K. J., Patil, C. K., Wodicka, L., Lockhart, D. J., Weissman, J. S., and Walter, P. (2000) Functional and genomic analyses reveal an essential coordianation between the unfolded protein response and ER-associated degradation. Cell 101, 249–258.

    PubMed  CAS  Google Scholar 

  46. Friedlander, R., Jarosch, E., Urban, J., Volkwein, C., and Sommer, T. (2000) A regulatory link between ER-associated protein degradation and the unfolded-protein response. Nat. Cell Biol. 2, 379–384.

    PubMed  CAS  Google Scholar 

  47. High, S., Lecomte, F. J., Russell, S. J., Abell, B. M., and Oliver, J. D. (2000) Glycoprotein folding in the endoplasmic reticulum: a tale of three chaperones?. FEBS Lett. 476, 38–41.

    PubMed  CAS  Google Scholar 

  48. Hammond, C. and Helenius, A. (1994) Quality control in the secretory pathway: retention of a misfolded viral membrane glycoprotein involves cycling between the ER, intermediate compartment, and Golgi apparatus. J. Cell Biol. 126, 41–52.

    PubMed  CAS  Google Scholar 

  49. Hebert, D. N., Foellmer, B., and Helenius, A. (1995) Glucose trimming and reglucosylation determine glycoprotein association with calnexin in the endoplasmic reticulum. Cell 81, 425–433.

    PubMed  CAS  Google Scholar 

  50. Ware, F. E., Vassilakos, A., Peterson, P. A., Jackson, M. R., Lehrman, M. A., and Williams, D. B. (1995) The molecular chaperone calnexin binds Glc1Man9GlcNAc2 oligosaccharide as an initial step in recognizing unfolded glycoproteins. J. Biol. Chem. 270, 4697–4704.

    PubMed  CAS  Google Scholar 

  51. Peterson, J. R., Ora, A., Van, P. N., and Helenius, A. (1995) Transient, lectin-like association of calreticulin with folding intermediates of cellular and viral glycoproteins. Mol. Biol. Cell 6, 1173–1184.

    PubMed  CAS  Google Scholar 

  52. Wada, I., Kai, M., Imai, S., Sakane, F., and Kanoh, H. (1997) Promotion of transferrin folding by cyclic interactions with calnexin and calreticulin. EMBO J. 16, 5420–5432.

    PubMed  CAS  Google Scholar 

  53. Zapun, A., Petrescu, S. M., Rudd, P. M., Dwek, R. A., Thomas, D. Y., and Bergeron, J. J. (1997) Conformation-independent binding of monoglucosylated ribonuclease B to calnexin. Cell 88, 29–38.

    PubMed  CAS  Google Scholar 

  54. Cannon, K. S. and Helenius, A. (1999) Trimming and readdition of glucose to N-linked oligosaccharides determines calnexin association of a substrate glycoprotein in living cells. J. Biol. Chem. 274, 7537–7544.

    PubMed  CAS  Google Scholar 

  55. Labriola, C., Cazzulo, J. J., and Parodi, A. J. (1999) Trypanosoma cruzi calreticulin is a lectin that binds monoglucosylated oligosacharides but not protein moieties of glycoproteins. Mol. Biol. Cell. 10, 1381–1394.

    PubMed  CAS  Google Scholar 

  56. Radcliffe, C. M., Diedrich, G., Harvey, D. J., Dwek, R. A., Cresswell, P., and Rudd, P. M. (2002) Identification of specific glycoforms of major histocompatibility complex class I heavy chains suggests that class I peptide loading is an adaptation of the quality control pathway involving calreticulin and ERp57. J. Biol. Chem. 277, 46415–46423.

    PubMed  CAS  Google Scholar 

  57. Saito, Y., Ihara, Y., Leach, M. R., Cohen-Doyle, M. F., and Williams, D. B. (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 

  58. Ihara, Y., Cohen-Doyle, M. F., Saito, Y., and Williams, D. B. (1999) Canexin discriminates between protein conformational states and functions as a molecular chaperone in vitro. Mol. Cell 4, 331–341.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  60. Oliver, J. D., Roderick, H. L., Llewellyn, D. H., and High, S. (1999) ERp57 functions as a subunit of specific complexes formed with the ER lectins calreticulin and calnexin. Mol. Biol. Cell 10, 2573–2582.

    PubMed  CAS  Google Scholar 

  61. Elliott, J. G., Oliver, J. D., and High, S. (1997) The thiol-dependent reductase ERp57 interacts specifically with N-glycosylated integral membrane proteins. J. Biol. Chem. 272, 13849–13855.

    PubMed  CAS  Google Scholar 

  62. Van der Wal, F. J., Oliver, J. D., and High, S. (1998) The transient association of ERp57 with N-glycosylated proteins is regulated by glucose trimming. Eur. J. Biochem. 256, 51–59.

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  64. Kang, S. J. and Cresswell, P. (2002), Calnexin, calreticulin and ERp57 cooperate in disulfide bond formation in human CD1d heavy chain. J. Biol. Chem. 277, 44838–44844.

    PubMed  CAS  Google Scholar 

  65. Van Leeuwen, J. E., and Kearse, K. P. (1997) Reglucosylation of N-linked glycans is critical for calnexin assembly with T cell receptor (TCR) alpha proteins but not TCRbeta proteins. J. Biol. Chem. 272, 4179–4186.

    PubMed  Google Scholar 

  66. Ritter, C. and Helenius, A. (2000) Recognition of local glycoprotein misfolding by the ER folding sensor UDP-glucose:glucoprotein glucosyltransferase. Nature Struct. Biol. 7, 278–280.

    PubMed  CAS  Google Scholar 

  67. Otteken, A. and Moss, B. (1996) Calreticulin interacts with newly synthesized human immunodeficiency virus type 1 envelope glycoprotein, suggesting a chaperone function similar to that of calnexin. J. Biol. Chem. 271, 97–103

    PubMed  CAS  Google Scholar 

  68. Li, Y., Bergeron, J. J., Luo, L., Ou, W. J., Thomas, D. Y., and Kang, C. Y. (1996) Effects of inefficient cleavage of the signal sequence of inefficient cleavage of the signal sequence of HIV-1 gp 120 on its association with calnexin, folding, and intracellular transport. Proc. Natl. Acad. Sci. USA 93, 9606–9611.

    PubMed  CAS  Google Scholar 

  69. Li, Y., Luo, L., Thomas, D. Y., and Kang, C. Y. (2000) The HIV-1 Env protein signal sequence retards its cleavage and down-regulates the glycoprotein folding. Virology 272, 417–428.

    PubMed  CAS  Google Scholar 

  70. Land, A., and Braakman, I. (2001) Folding of the human immunodeficiency virus type 1 envelope glycoprotein in the endoplasmic reticulum. Biochimie 83, 783–790.

    PubMed  CAS  Google Scholar 

  71. Hochstenbach, F., David, V., Watkins, S., and Brenner, M. B. (1992), Endoplasmic reticulum resident protein of 90 kilodaltons associates with the T- and B-cell antigen receptors and major histocompatibility complex antigens during their assembly. Proc. Natl. Acad. Sci. USA 89, 4734–4738.

    PubMed  CAS  Google Scholar 

  72. Ortmann, B., Androlewicz, M. J., and Cresswell, P. (1994). MHC class I/beta 2-microglobulin complexes associate with TAP transporters before peptide binding. Nature 368, 864–867.

    PubMed  CAS  Google Scholar 

  73. Sadasivan, B., Lehner, P. J., Oxtmann, B., Spies, T., and Cresswell, P. (1996) Roles for calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class I molecules with TAP. Immunity 5, 103–114.

    PubMed  CAS  Google Scholar 

  74. van Leeuwen, J. E. and Kearse, K. P. (1996) Deglucosylation of N-linked glycans is an important step in the dissociation of calreticulin-class I-TAP complexes. Proc. Natl. Acad. Sci. USA 93, 13997–14001.

    PubMed  Google Scholar 

  75. Vassilakos, A., Cohen-Doyle, M. F., Peterson, P. A., Jackson, M. R., and Williams, D. B. (1996) The molecular chaperone calnexin facilitates folding and assembly of class I histocompatibility molecules. EMBO J. 15, 1495–1506.

    PubMed  CAS  Google Scholar 

  76. Gao, B., Adhikari, R., Howarth, M., Nakamura, K., Gold, M. C., Hill, A. B., et al. (2002) Assembly and antigen-presenting function of MHC class I molecules in cells lacking the ER chaperone calreticulin. Immunity 16, 99–109.

    PubMed  CAS  Google Scholar 

  77. Williams, A., Peh, C. A., and Elliott, T. (2002) The cell biology of MHC class I antigen presentation. Tissue Antigens 59, 3–17.

    PubMed  CAS  Google Scholar 

  78. van Leeuwen, J. E. and Kearse, K. P. (1996) Calnexin associates exclusively with individual CD3 delta and T cell antigen receptor (TCR) alpha proteins containing incompletely trimmed glycans that are not assembled into multisubunit TCR complexes. J. Biol. Chem. 271, 9660–9665.

    PubMed  Google Scholar 

  79. Le, A., Steiner, J. L., Ferrell, G. A., Shaker, J. C., and Sifers, R. N. (1994) Association between calnexin and a secretion-incompetent variant of human alpha 1-antitrypsin. J. Biol. Chem. 269, 7514–7519.

    PubMed  CAS  Google Scholar 

  80. Liu, Y., Choudhury, P., Cabral, C. M. and Sifers, R. N. (1997) Intracellular disposal of incompletely folded human alpha1-antitrypsin involves release from calnexin and post-translational trimming of asparaginelinked oligosaccharides. J. Biol. Chem. 272, 7946–7951.

    PubMed  CAS  Google Scholar 

  81. Halaban, R., Cheng, E., Zhang, Y., Moellmann, G., Hanlon, D., Michalak, M., et al. (1997) Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme contributes to the dedifferentiated phenotype of amelanotic melanoma cells. Proc. Natl. Acad. Sci. USA 94, 6210–6215.

    PubMed  CAS  Google Scholar 

  82. Halaban, R., Svedine, S., Cheng, E., Smicun, Y., Aron, R., and Hebert, D. N. (2000) Endoplasmic reticulum retention is a common defect associated with tyrosinase-negative albinism. Proc. Natl. Acad. Sci. USA 97, 5889–5894.

    PubMed  CAS  Google Scholar 

  83. Branza-Nichita, N., Negroiu, G., Petrescu, A. J., Garman, E. F., Platt, F. M., Wormald, M. R., et al. (2000) Mutations at critical N-glycosylation sites reduce tyrosinase activity by altering folding and quality control. J. Biol. Chem. 275, 8169–8175.

    PubMed  CAS  Google Scholar 

  84. Capellari, S., Zaidi, S. I., Urig, C. B., Perry, G., Smith, M. A., and Petersen, R. B. (1999) Prien protein glycosylation is sensitive to redox change. J. Biol. Chem. 274,34846–34850.

    PubMed  CAS  Google Scholar 

  85. Rudd, P. M., Wormald, M. R., Wing, D. R., Prusiner, S. B., and Dwek, R. A. (2001) Prion glycoprotein: structure, dynamics, and roles for the sugars. Biochemistry 40, 3759–3766.

    PubMed  CAS  Google Scholar 

  86. Pind, S., Riordan, J. R., and Williams, D. B. (1994) Participation of the endoplasmic reticulum chaperone calnexin (p88, IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 269, 12784–12788.

    PubMed  CAS  Google Scholar 

  87. Loo, M. A., Jensen, T. J., Cui, L., Hou, Y., Chang, X. B., and Riordan, J. R. (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 

  88. Cressell, P. (2000) Intracellular surveillance: controlling the assembly of MHC class I-peptide complexes. Traffic 1, 301–305.

    Google Scholar 

  89. Diedrich, G., Bangia, N., Pan, M., and Cresswell, P. (2001) A role for calnexin in the assembly of the MHC class I loading complex in the endoplasmic reticulum. J. Immunol. 166, 1703–1709.

    PubMed  CAS  Google Scholar 

  90. Hebert, D. N., Zhang, J. X., Chen, W., Foellmer, B., and 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 

  91. Wada, I., Imai, S., Kai, M., Sakane, F., and Kanoh, H. (1995) Chaperone function of calreticulin when expressed in the endoplasmic reticulum as the membrane-anchored and soluble forms. J. Biol. Chem. 270, 20298–20304.

    PubMed  CAS  Google Scholar 

  92. Ho, S. C., Rajagopalan, S., Chaudhuri, S., Shieh, C. C., Brenner, M. B., and Pillai, S. (1999) Membrane anchoring of calnexin facilitates its interaction with its targets. Mol. Immunol. 36, 1–12.

    PubMed  CAS  Google Scholar 

  93. Danilczyk, U. G., Cohen-Doyle, M. F., and Williams, D. B. (2000) Functional relationship between calreticulin, calnexin, and the endoplasmic reticulum luminal domain of calnexin. J. Biol. Chem. 275, 13089–13097.

    PubMed  CAS  Google Scholar 

  94. Rodan, A. R., Simons, J. F., Trombetta, E. S., and Helenius, A. (1996) N-linked oligosaccharides are necessary and sufficient for association of glycosylated forms of bovine RNase with calnexin and calreticulin. EMBO J. 15, 6921–6930.

    PubMed  CAS  Google Scholar 

  95. Stronge, V. S., Saito, Y., Ihara, Y., and Williams, D. B. (2001) Relationship between calnexin and BiP in suppressing aggregation and promoting refolding of protein and glycoprotein substrates. J. Biol. Chem. 276, 39779–39787.

    PubMed  CAS  Google Scholar 

  96. Michalak, M., Corbett, E. F., Mesaeli, N., Nakamura, K., and Opas, M. (1999) Calreticulin: one protein, one gene, many functions. Biochem. J. 144 Pt 2 281–292.

    Google Scholar 

  97. Corbett, E. F. and Michalak, M. (2000) Calcium, a signaling molecule in the endoplasmic reticulum? Trends Biochem. Sci. 25, 307–311.

    PubMed  CAS  Google Scholar 

  98. Mesaeli, N., Nakamura, K., Zvaritch, E., Dickie, P., Dziak, E., Krause, K. H., et al. (1999) Calreticulin is essential for cardiac development. J. Cell Biol. 144, 857–868.

    PubMed  CAS  Google Scholar 

  99. Li, J., Puceat, M., Perez-Terzic, C., Mery, A., Nakamura, K., Michalak, M., et al. (2002) Calreticulin reveals a critical Ca(2+) checkpoint in cardiac myofibrillogenesis. J. Cell Biol. 158, 103–113.

    PubMed  CAS  Google Scholar 

  100. Guo, L., Nakamura, K., Lynch, J., Opas, M., Olson, E. N., Agellona, L. B., et al. (2002) Cardiac specific expression of calcineurin reverses embryonic lethality in calreticulindeficient mouse. J. Biol. Chem. 277, 50776–50779.

    PubMed  CAS  Google Scholar 

  101. Wada, I., Rindress, D., Cameron, P. H., Ou, W. J., Doherty, J. J., 2nd, Louvard, D., et al. (1991) SSR alpha and associated calnexin are major calcium binding proteins of the endoplasmic reticulum membrane. J. Biol. Chem. 266, 19599–19610.

    PubMed  CAS  Google Scholar 

  102. Tjoelker, L. W., Seyfried, C. E., Eddy, R. L., Jr., Byers, M. G., Shows, T. B., Calderon, J., et al. (1994) Human, mouse, and rat calnexin cDNA cloning: identification of potential calcium binding motifs and gene localization to human chromosome 5. Biochemistry 33, 3229–3236.

    PubMed  CAS  Google Scholar 

  103. Denzel, A., Molinari, M., Trigueros, C., Martin, J. E., Velmurgan, S., Brown, S., et al. (2002) Early postnatal death and motor disorders in mice congenitally deficient incalnexin expression. Mol. Cell Biol. 22, 7398–7404.

    PubMed  CAS  Google Scholar 

  104. Fliegel, L., Burns, K., MacLennan, D. H., Reithmeier, R. A., and Michalak, M. (1989) Molecular cloning of the high affinity calciumbinding protein (calreticulin) of skeletal muscle sarcoplasmic reticulum. J. Biol. Chem. 264, 21522–21528.

    PubMed  CAS  Google Scholar 

  105. Smith, M. J. and Koch, G. L. (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 

  106. Baksh, S., and Michalak, M. (1991) Expression of calreticulin in Escherichia coli and identification of its Ca2+ binding domains. J. Biol. Chem. 266, 21458–21465.

    PubMed  CAS  Google Scholar 

  107. Michalak, M., Milner, R. E., Burns, K., and Opas, M. (1992) Calreticulin. Biochem. J. 285, 681–692

    PubMed  CAS  Google Scholar 

  108. Ostwald, T. J., and MacLennan, D. H. (1974) Isolation of a high affinity calcium-binding protein from sarcoplasmic reticulum. J. Biol. Chem. 249, 974–979.

    PubMed  CAS  Google Scholar 

  109. Khanna, N. C., Tokuda, M., and Waisman, D. M. (1986) Conformational changes induced by binding of divalent cations to calregulin. J. Biol. Chem. 261, 8883–8887.

    PubMed  CAS  Google Scholar 

  110. Schrag, J. D., Bergeron, J. J., Li, Y., Borisova, S., Hahn, M., Thomas, D. Y., et al. (2001), The structure of calnexin, an ER chaperone involved in quality control of protein folding. Mol. Cell 8 633–644.

    PubMed  CAS  Google Scholar 

  111. Houen, G. and Koch, C. (1994) Human placental calreticulin: purification, characterization and association with other proteins. Acta. Chem. Scand. 48, 905–911.

    Article  PubMed  CAS  Google Scholar 

  112. Ou, W. J., Thomas, D. Y., Bell, A. W., and Bergeron, J. J. (1992) Casein kinase II phosphorylation of signal sequence receptor alpha and the associated membrane chaperone calnexin. J. Biol. Chem. 267, 23789–23796.

    PubMed  CAS  Google Scholar 

  113. Wong, H. N., Ward, M. A., Bell, A. W., Chevet, E., Bains, S., Blackstock, W. P., et al. (1998) Conserved in vivo phosphorylation of calnexin at casein kinase II sites as well as a protein kinase C/proline-directed kinase site. J. Biol. Chem. 273, 17227–17235.

    PubMed  CAS  Google Scholar 

  114. Chevet, E., Wong, H. N., Gerber, D., Cochet, C., Fazel, A., Cameron, P. H., et al. (1999) Phosphorylation by CK2 and MAPK enhances calnexin association with ribosomes. EMBO J. 18, 3655–3666.

    PubMed  CAS  Google Scholar 

  115. Ikawa, M., Wada, I., Kominami, K., Watanabe, D., Toshimori, K., Nishimune, Y., et al. (1997) The putative chaperone calmegin is required for sperm fertility. Nature 387, 607–611.

    PubMed  CAS  Google Scholar 

  116. Ikawa, M., Nakanishi, T., Yamada, S., Wada, I., Kominami, K., Tanaka, H., et al. (2001) Calmegin is required for fertilin alpha/beta heterodimerization and sperm fertility. Dev. Biol. 240, 254–261.

    PubMed  CAS  Google Scholar 

  117. Persson, S., Rosenquist, M., and Sommarin, M. (2002) Identification of a novel calreticulin isoform (Crt2) in human and mouse. Gene 297, 151–158.

    PubMed  CAS  Google Scholar 

  118. Ohsako, S., Hayashi, Y., and Bunick, D. (1994) Molecular cloning and sequencing of calnexint. An abundant male germ cell-specific calcium-binding protein of the endoplasmic reticulum. J. Biol. Chem. 269, 14140–14148.

    PubMed  CAS  Google Scholar 

  119. Watanabe, D., Yamada, K., Nishina, Y., Tajima, Y., Koshimizu, U., Nagata, A., et al. (1994) Molecular cloning of a novel Ca(2+)-binding protein (calmegin) specifically expressed during male meiotic germ cell development. J. Biol. Chem. 269, 7744–7749.

    PubMed  CAS  Google Scholar 

  120. Cala, S. E., Ulbright, C., Kelley, J. S., and Jones, L. R. (1993) Purification of a 90-kDa protein (Band VII) from cardiac sarcoplasmic reticulum. Identification as calnexin and localization of casein kinase II phosphorylation sites. J. Biol. Chem. 268, 2969–2975.

    PubMed  CAS  Google Scholar 

  121. Ou, W. J., Bergeron, J. J., Li, Y., Kang, C. Y., and Thomas, D. Y. (1995), Conformation changes induced in the endoplasmic reticulum luminal domain of calnexin by Mg-ATP and Ca2+. J. Biol. Chem. 270, 18051–18059.

    PubMed  CAS  Google Scholar 

  122. Waisman, D. M., Salimath, B. P., and Anderson, M. J. (1985) Isolation and characterization of CAB-63, a novel calcium-binding protein. J. Biol. Chem. 260, 1652–1660.

    PubMed  CAS  Google Scholar 

  123. Corbett, E. F., Oikawa, K., Francois, P., Tessier, D. C., Kay, C., Bergeron, J. J., et al. (1999) Ca2+ regulation of interactions between endoplasmic reticulum chaperones. J. Biol. Chem. 274, 6203–6211.

    PubMed  CAS  Google Scholar 

  124. Corbett, E. F., Michalak, K. M., Oikawa, K., Johnson, S., Campbell, I. D., Eggleton, P., et al. (2000) The conformation of calreticulin is influenced by the end oplasmic reticulum luminal environment. J. Biol. Chem. 275, 27177–27185.

    PubMed  CAS  Google Scholar 

  125. Li, Z., Stafford, W. F., and Bouvier, M. (2001) The metal ion binding properties of calreticulin modulate its conformational flexibility and thermal stability. Biochemistry 40, 11193–11201.

    PubMed  CAS  Google Scholar 

  126. Bouvier, M., and Stafford, W. F. (2000) Probing the three-dimensional structure of human calreticulin. Biochemistry 39, 14950–14959.

    PubMed  CAS  Google Scholar 

  127. Baksh, S., Spamer, C., Heilmann, C., and Michalak, M. (1995) Identification of the Zn2+ binding region in calreticulin. FEBS Lett. 376, 53–57.

    PubMed  CAS  Google Scholar 

  128. Leach, M. R., Cohen-Doyle, M. F., Thomas, D. Y., and Williams, D. B. (2002) Localization of the Lectin, ERp57 Binding, and Polypeptide Binding Sites of Calnexin and Calreticulin. J. Biol. Chem. 277, 29686–29697.

    PubMed  CAS  Google Scholar 

  129. Borrelly, G. P., Harrison, M. D., Robinson, A. K., Cox, S. G., Robinson, N. J., and Whitehall, S. K. (2002) Surplus zinc is handled by Zym1 metallothionein and Zhf endoplasmic reticulum transporter in Schizosaccharomyces pombe. J. Biol. Chem. 277, 30394–30400.

    PubMed  CAS  Google Scholar 

  130. Clemens, S., Bloss, T., Vess, C., Neumann, D., Nies, D. H., and Zur Nieden, U. (2002) A transporter in the endoplasmic reticulum of Schizosaccharomyces pombe cells mediates zinc storage and differentially affects transition metal tolerance. J. Biol. Chem. 277, 18215–18221.

    PubMed  CAS  Google Scholar 

  131. Vassilakos, A., Michalak, M., Lehrman, M. A., and Williams, D. B. (1998) Oligosaccharide binding characteristics of the molecular chaperones calnexin and calreticulin. Biochemistry 37, 3480–3490.

    PubMed  CAS  Google Scholar 

  132. Wei, J., and Hendershot, L. M., (1995) Characterization of the nucleotide binding properties and ATPase activity of recombinant hamster BiP purified from bacteria. J. Biol. Chem. 270, 26670–26676.

    PubMed  CAS  Google Scholar 

  133. Spiro, R. G., Zhu, Q., Bhoyroo, V., and Soling, H. D. (1996) 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.

    PubMed  CAS  Google Scholar 

  134. Peterson, J. R., and Helenius, A. (1999) In vitro reconstitution of calreticulin-substrate interactions. J. Cell Sci. 112, 2775–2784.

    PubMed  CAS  Google Scholar 

  135. Kapoor, M., Srinivas, H., Kandiah, E., Gemma, E., Ellgaard, L., Oscarson, S., et al. (2003) Interactions of substrate with calreticulin, an endoplasmic reticulum chaperone. J. Biol. Chem. 278, 6194–6200.

    PubMed  CAS  Google Scholar 

  136. Petrescu, A. J., Butters, T. D., Reinkensmeier, G., Petrescu, S., Platt, F. M., Dwek, R. A., et al. (1997) The solution NMR structure of glucosylated N-glycans involved in the early stages of glycoprotein biosynthesis and folding. EMBO J. 16, 4302–4310.

    PubMed  CAS  Google Scholar 

  137. Patil, A. R., Thomas, C. J., and Surolia, A. (2000) Kinetics and the mechanism of interaction of the endoplasmic reticulum chaperone, calreticulin, with monoglucosylated (Glc1Man9GlcNAc2) substrate. J. Biol. Chem. 275, 24348–24356.

    PubMed  CAS  Google Scholar 

  138. Di Jeso, B., Ulianich, L., Pacifico, F., Leonardi, A., Vito, P., Consiglio, E., et al., (2002) The folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by a loss of Ca2+ from the endoplasmic reticulum. Biochem. J. 370, 449–458.

    Google Scholar 

  139. Rudenko G., Nguyen, T., Chelliah, Y., Sudhof, T. C., and Deisenhofer, J. (1999) The structure of the ligand-binding domain of neurexin Ibeta: regulation of LNS domain function by alternative splicing. Cell 99, 93–101.

    PubMed  CAS  Google Scholar 

  140. Ellgaard, L., Riek, R., Herrmann, T., Güntert, P., Braun, D., Helenius, A., et al. (2001) NMR structure of the calreticulin P-domain. Proc. Natl. Acad. Sci. USA 98, 3133–3138.

    PubMed  CAS  Google Scholar 

  141. Ellgaard, L., Riek, R., Braun, D., Herrmann T., Helenius, A., and Wüthrich, K. (2001) Three-dimensional structure topology of the calreticulin P-domain based on NMR assignment. FEBS Lett. 488, 69–73.

    PubMed  CAS  Google Scholar 

  142. Ellgaard, L., Bettendorff, P., Braun, D., Herrmann, T., Fiorito, F., Jelesarov, I., et al. (2002) NMR Structures of 36 and 73-residue Fragments of the Calreticulin P-domain. J. Mol. Biol. 322, 773–784.

    PubMed  CAS  Google Scholar 

  143. Frickel, E.-M., Riek, R., Jelesarov, I., Helenius, A., Wüthrich, K., and Ellgaard, L. (2002) TROSY-NMR reveals interaction between ERp57 and the tip of the calreticulin P-domain. Proc. Natl. Acad. Sci. USA 99, 1954–1959.

    PubMed  CAS  Google Scholar 

  144. Fassio, A. and Sitia, R. (2002) Formation, isomerisation and reduction of disulphide bonds during protein quality control in the endoplasmic reticulum. Histochem. Cell Biol. 117, 151–157.

    PubMed  CAS  Google Scholar 

  145. Freedman, R. B., Klappa, P., and Ruddock, L. W. (2002) Protein disulfide isomerases exploit synergy between catalytic and specific binding domains. EMBO Rep. 3, 136–140.

    PubMed  CAS  Google Scholar 

  146. Bennett, C. F., Balcarek, J. M., Varrichio, A., and Crooke, S. T. (1988) Molecular cloning and complete amino-acid sequence of form-1 phosphoinositide-specific phospholipase C. Nature 334, 268–270.

    PubMed  CAS  Google Scholar 

  147. Klappa, P., Ruddock, L. W., Darby, N. J., and Fredman, R. B. (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 

  148. Pirneskoski, A., Ruddock, L. W., Klappa, P., Freedman, R. B., Kivirikko K. I., and Koivunen P. (2001) Domains b′ and a′ of protein disulfide isomerase fulfill the minimum requirement for function as a subunit of prolyl 4-hydroxylase. The N- terminal domains a and b enhances this function and can be substituted in part by those of ERp57. J. Biol. Chem. 276, 11287–11293.

    PubMed  CAS  Google Scholar 

  149. Kemmink, J., Darby, N. J., Dijkstra, K., Nilges, M., and Creighton, T. E. (1996) Structure determination of protein disulfide isomerase using multidimensional heteronuclear 13C/15N NMR spectroscopy. Biochemistry 35, 7684–7691.

    PubMed  CAS  Google Scholar 

  150. Kemmink, J., Dijkstra, K., Mariani, M., Scheek, R. M., Penka, E., Nilges, M., et al. (1999) The structure in solution of the b domain of protein disulfide isomerase. J. Biomol. NMR 13, 357–368.

    PubMed  CAS  Google Scholar 

  151. Silvennoinen, L., Karvonen, P., Koivunen, P., Myllyharju, J., Kivirikko, K., and Kilpelainen, I. (2001) Assignment of 1H, 13C and 15N resonances of the a′ domain of ERp57. J. Biomol. NMR 20, 385–386.

    PubMed  CAS  Google Scholar 

  152. Srivastava, S. R., Fuchs, J. A., and Holtzman, J. L. (1993) The reported cDNA sequence for phospholipase C alpha encodes protein disulfide isomerase, isozyme Q-2 and not phospholipase-C. Biochem. Biophys. Res. Commun. 193, 971–978.

    PubMed  CAS  Google Scholar 

  153. Hirano, N., Shibasaki, F., Sakai, R., Tanaka, T., Nishida, J., Yazaki, Y., et al. (1995) Molecular cloning of the human glucose-regulated protein ERP57/GRP58, a thiol-dependent reductase. Identification of its secretory form and inducible expression by the oncogenic transformation. Eur. J. Biochem. 234, 336–342.

    PubMed  CAS  Google Scholar 

  154. Bonfils, C. (1998) Purification of a 58-kDa protein (ER58) from monkey liver microsomes and comparison with protein-disulfide isomerase. Eur. J. Biochem. 254, 420–427.

    PubMed  CAS  Google Scholar 

  155. Bourdi, M., Demady, D., Martin, J. L., Jabbour, S. K., Martin, B. M., George, J. W., et al. (1995) cDNA cloning and baculovirus expression of the human liver endoplasmic reticulum P58: characterization as a protein disulfide isomerase isoform, but not as a protease or a carnitine acyltransferase. Arch. Biochem. Biophys. 323, 397–403.

    PubMed  CAS  Google Scholar 

  156. Antoniou, A. N., Ford, S., Alphey, M., Osborne, A., Elliott, T., and Powis, S. J. (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 

  157. Zapun, A., Darby, N. J., Tessier, D. C., Michalak, M., Bergeron, J. J., and Thomas, D. Y. (1998) Enhanced catalysis of ribonuclease B folding by the interaction of calnexin or calreticulin with ERp57. J. Biol. Chem. 273, 6009–6012.

    PubMed  CAS  Google Scholar 

  158. Elliott, J. G., Oliver, J. D., Volkmer, J., Zimmermann, R., and High, S. (1998) In vitro characterisation of the interaction between newly synthesised proteins and a pancreatic isoform of protein disulphide isomerase. Eur. J. Biochem. 252, 372–377.

    PubMed  CAS  Google Scholar 

  159. baksh, S., Burns, K., Andrin, C., and Michalak, M. (1995) Interaction of calreticulin with protein disulfide isomerase. J. Biol. Chem. 270, 31338–31344.

    PubMed  CAS  Google Scholar 

  160. Keller, S. H., Lindstrom, J., and Taylor, P. (1998) Inhibition of glucose trimming with castanospermine reduces calnexin association and promotes proteasome degradation of the alpha-subunit of the nicotinic acetylcholine receptor. J. Biol. Chem. 273, 1706417072.

    Google Scholar 

  161. Allen, S., Goodeve, A. C., Peake, I. R., and Daly, M. E. (2001) Endoplasmic reticulum retention and prolonged association of a von Willebrand's disease-causing von Willebrand factor variant with ERp57 and calnexin. Biochem. Biophys. Res. Commun. 280, 448–453.

    PubMed  CAS  Google Scholar 

  162. Tamura, T., Yamashita, T., Segawa, H., and Taira, H. (2002) N-linked oligosaccharide chains of Sendai virus fusion protein determine the interaction with endoplasmic reticulum molecular chaperones. FEBS Lett. 513, 153–158.

    PubMed  CAS  Google Scholar 

  163. Van Kaer, L. (2002) Major histocompatibility complex classI-restricted antigen processing and presentation. Tissue Antigens 60, 1–9.

    PubMed  Google Scholar 

  164. Bouvier, M. (2003) Accessory proteins and the assembly of human class 1 MHC molecules: a molecular and structural perspective. Mol. Immunol. 39, 697–706.

    PubMed  CAS  Google Scholar 

  165. Smith, J. D., Solheim, J. C., Carreno, B. M., and Hansen, T. H. (1995) Characterization of class I MHC folding intermediates and their disparate interactions with peptide and beta 2-microglobulin. Mol. Immunol. 32, 531–540.

    PubMed  CAS  Google Scholar 

  166. Tector, M., Zhang, Q., and Salter, R. D. (1997) Beta 2-microglobulin and calnexin can independently promote folding and disulfide bond formation in class I histocompatibility proteins. Mol. Immunol. 34, 401–408.

    PubMed  CAS  Google Scholar 

  167. Farmery, M. R., Allen, S., Allen, A. J., and Bulleid, N. J. (2000) The role of ERp57 in disulfide bond formation during the assembly of major histocompatibility complex class I in a synchronized semipermeabilized cell translation system. J. Biol. Chem. 275, 14933–14938.

    PubMed  CAS  Google Scholar 

  168. Morrice, N. A. and Powis, S. J. (1998) A role for the thiol-dependent reductase ERp57 in the assembly of MHC class I molecules. Curr. Biol. 8, 713–716.

    PubMed  CAS  Google Scholar 

  169. Hughes, E. A. and Cresswell, P. (1998) The thiol oxidoreductase ERp57 is a component of the MHC class I peptide-loading complex. Curr. Biol. 8, 709–712.

    PubMed  CAS  Google Scholar 

  170. Lindquist, J. A., Jensen, O. N., Mann, M., and Hammerling, G. J. (1998) ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class I assembly. EMBO J. 17, 2186–2195.

    PubMed  CAS  Google Scholar 

  171. Harris, M. R., Lybarger, L., Yu, Y. Y., Myers, N. B., and Hansen, T. H. (2001) Association of ERp57 with mouse MHC class I molecules is tapasin dependent and mimics that of calreticulin and not calnexin. J. Immunol. 166, 6686–6692.

    PubMed  CAS  Google Scholar 

  172. Dick, T. P., Bangia, N., Peaper, D. R., and Cresswell, P. (2002) Disulfide bond isomerization and the assembly of MHC class I-peptide complexes. Immunity 16, 87–98.

    PubMed  CAS  Google Scholar 

  173. Ellgaard, L., and Helenius, A. (2001) ER quality control: towards an understanding at the molecular level. Curr. Opin. Cell Biol. 13, 431–437.

    PubMed  CAS  Google Scholar 

  174. Zhang, Q., Tector, M., and Salter, R. D. (1995) Calnexin recognizes carbohydrate and protein determinants of class I major histocompatibility complex molecules. J. Biol. Chem. 270, 3944–3948.

    PubMed  CAS  Google Scholar 

  175. Bennett, M. J., Van Leeuwen, J. E., and Kearse, K. P. (1998) calnexin association is not sufficient to protect T cell receptor alpha proteins from rapid degradation in CD4+CD8+ thymocytes. J. Biol. Chem. 273, 23674–23680.

    PubMed  CAS  Google Scholar 

  176. Danilczyk, U. G. and Williams, D. B. (2001) The lectin chaperone calnexin utilizes polypeptide-based interactions to associate with many of its substrates in vivo. J. Biol. Chem. 276, 25532–25540.

    PubMed  CAS  Google Scholar 

  177. Ora, A., and Helenius, A. (1995) Calnexin fails to associate with substrate proteins in glucosidase-deficient cell lines. J. Biol. Chem. 270, 26060–26062.

    PubMed  CAS  Google Scholar 

  178. Suh, K., Bergmann, J. E., and Gabel, C. A. (1989) Selective retention of monoglucosylated high mannose oligosaccharides by a class of mutant vesicular stomatitis virus G proteins. J. Cell Biol. 108, 811–819.

    PubMed  CAS  Google Scholar 

  179. Koradi, R., Billeter, M., and Wüthrich, K. (1996) MOLMOL: A program for display and analysis of macromolecular structures. J. Mol. Graph. 14, 51–55.

    PubMed  CAS  Google Scholar 

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Ellgaard, L., Frickel, EM. Calnexin, calreticulin, and ERp57. Cell Biochem Biophys 39, 223–247 (2003). https://doi.org/10.1385/CBB:39:3:223

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