, Volume 50, Issue 11–12, pp 1012–1020

BiP (GRP78), an essential hsp70 resident protein in the endoplasmic reticulum

  • I. G. Haas
Multi-Author Reviews


BiP is a constitutively-expressed resident protein of the endoplasmic, reticulum (ER) of all eucaryotic cells, and belongs to the highly conserved hsp70 protein family. In the ER, BiP is involved in polypeptide translocation, protein folding and presumably protein degradation as well. These functions are essential to cell viability, as has been shown for yeast. In this review, I will summarize the structural features of hsp70 proteins and focus on those experiments which revealed the biological function of BiP.

Key words

ER-translocation folding and assembly of polypeptide chains hsp70 structure ER-degradation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Beckman, R. P., Mizzen, L. A., and Welch, W. J., Interaction of hsp70 with newly synthesized proteins: implications for protein folding and assembly. Science246 (1990) 850–854.Google Scholar
  2. 2.
    Blond-Elguindi, S., Cwirla, S. E., Dower, W. J., Lipshutz, R. J., Sprang, S. R., Sambrook, J. F., and Gething, M.-J. H., Affinity panning of a library of peptides displayed on bacteriophages reveals the binding specificity of BiP. Cell75 (1993) 717–728.PubMedGoogle Scholar
  3. 3.
    Bole, D. G., Hendershot, L., and Kearney, J. F., Posttranslational association of immunoglobulin heavy chain binding protein with nascent heavy chain in nonsecreting and secreting hybridomas. J. Cell Biol.102, (1986) 1558–1566.PubMedGoogle Scholar
  4. 4.
    Bork, P., Sander, C., and Valencia, A., An ATPase domain common to prokaryotic cell cycle proteins, sugar kinases, actin, and hsp70 heat shock proteins. Proc. natl Acad. Sci. USA89 (1992) 7290–4.PubMedGoogle Scholar
  5. 5.
    Braakman, I., Helenius, J., and Helenius, A., Manipulating disulfide bond formation and protein folding in the endoplasmic reticulum. EMBO J.11 (1992) 1717–1722.PubMedGoogle Scholar
  6. 6.
    Braakman, I., Helenius, J., and Helenius, A., Role of ATP and disulfide fonds during protein folding in the endoplasmic reticulum. Nature356 (1992) 260–262.PubMedGoogle Scholar
  7. 7.
    Braell, W. A., Schlossman, D. M., Schmid, S. L., and Rothman, J. E., Dissociation of clathrin coats coupled to the hydrolysis of ATP; role of an uncoating ATPase. J Cell Biol.99 (1984) 734–741.PubMedGoogle Scholar
  8. 8.
    Brodsky, J. L., Hamamoto, S., Feldheim, D., and Schekman, R., Reconstruction of protein translocation from solubilized yeast membranes reveals topologically distinct roles for BiP and cytosolic Hsc70. J. Cell Biol.120 (1993) 95–102.PubMedGoogle Scholar
  9. 9.
    Brodsky, J. L., and Sheckman, R., A Sec63p-BiP complex from yeast is required for protein translocation in a reconstituted proteoliposome. J. Cell Biol.123 (1993) 1355–1363.PubMedGoogle Scholar
  10. 10.
    Bulleid, N. J., and Freedman, R. B., Defective co-translational formation of disulphide bonds in protein disulphide-isomerasedeficient microsomes. Nature335 (1988) 649–51.PubMedGoogle Scholar
  11. 11.
    Carlsson, L., and Lazarides, E., ADP-ribosylation of theMr83,000 stress-inducible and glucose-regulated protein in avian and mammalian cells: Modulation by heat shock and glucose starvation. Proc. natl Acad. Sci. USA80 (1983) 4664–4668.PubMedGoogle Scholar
  12. 12.
    Chappell, T. G., Konforti, B. B., Schmid, S. L., and Rothman, J. E., The ATPase core of a clathrin uncoating protein. J. biol. Chem.262 (1987) 746–751.PubMedGoogle Scholar
  13. 13.
    Chappell, T. G., and Welch, W. J., Schlossman, D. M., Palter, K. B., Schlesinger, M. J., and Rothman, J. E., Uncoating ATPase is a member of the 70 kilodalton family of stress proteins. Cell45 (1986) 3–13.PubMedGoogle Scholar
  14. 14.
    Clairmont, C. A., De Maio, A., and Hirschberg, C. B., Translocation of ATP into the lumen of rough endoplasmic reticulum drived vesicles and its binding to luminal proteins including BiP (GRP 78) and GRP 94. J. biol. Chem.267 (1992) 3983–90.PubMedGoogle Scholar
  15. 15.
    Cox J. S., Shamu, C. E., and Walter, P., Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell73 (1993) 1197–206.PubMedGoogle Scholar
  16. 16.
    Cremer, A., Knittler, M. R., and Haas, I. G. in: 44. Colloquium Mosbach 1993: Glyco- and Cellbiology, pp. 171–184. Eds F. Wieland and W. Reutter. Springer-Verlag, Berlin-Heidelberg-New York 1994.Google Scholar
  17. 17.
    de Silva, A., Balch, W. E., and Helenius, A., Quality control in the endoplasmic reticulum: folding and misfolding of vesicular stomatitis virus G protein in cells and in vitro. J. Cell Biol.111 (1990) 857–66.PubMedGoogle Scholar
  18. 18.
    Dorner, A. J., Bole, D. G., and Kaufman, R. J., The relationship of N-linked glycosylation and heavy chain-binding protein association with the secretion of glycoproteins. J. Cell Biol.105 (1987) 2665–74.PubMedGoogle Scholar
  19. 19.
    Earl, P. L., Moss, B., and Doms, R. W., Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein. J. Virol.65 (1991) 2047–55.PubMedGoogle Scholar
  20. 20.
    Ellis, R. J., van der Vies S. and Hemmingsen, S. M., The molecular chaperone concept. Biochem. Soc. Symp.55 (1989) 145–53.PubMedGoogle Scholar
  21. 21.
    Ellis, R. J., and van der Vies, S. M., Molecular chaperones. A. Rev. Biochem.60 (1991) 321–347.Google Scholar
  22. 22.
    Flaherty, K. M., DeLuca-Flaherty, C., and McKay, D. B., Three-dimensional structure of the ATPase fragment of a 70K heat-shock cognate protein. Nature346 (1990) 623–628.PubMedGoogle Scholar
  23. 23.
    Flynn, G. C., Chappell, T. G., and Rothman, J. E., Peptide binding and release by proteins implicated as catalysts of protein assembly. Science245 (1989) 385–90.PubMedGoogle Scholar
  24. 24.
    Flynn, G. C., Pohl, J., Flocco, M. T., and Rothman, J. E., Peptide-binding specificity of the molecular chaperone BiP. Nature353 (1991) 726–30.PubMedGoogle Scholar
  25. 25.
    Freiden, P. J., Gaut, J. R., and Hendershot, L. M., Interconversion of three differentially modified and assembled forms of BiP. EMBO J.11 (1992) 63–70.PubMedGoogle Scholar
  26. 26.
    Gaut, J. R., and Hendershot, L. M., The immunoglobulin-binding protein in vitro autophosphorylation site maps to a threonine within the ATP binding cleft but is not a detectable site of in vivo phosphorylation. J. biol. Chem.268 (1993) 12691–8.PubMedGoogle Scholar
  27. 27.
    Gaut, J. R., and Hendershot, L. M., Mutations within the nucleotide binding site of immunoglobulin-binding protein inhibit ATPase activity and interfere with release of immunoglobulin heavy chain. J. biol. Chem.268 (1993) 7248–55.PubMedGoogle Scholar
  28. 28.
    Gething, M.-J., McCammon, K., and Sambrook, J., Expression of wild-type and mutant forms of influenza hemagglutinin: The role of folding and intracellular transport. Cell46 (1986) 939–950.PubMedGoogle Scholar
  29. 29.
    Gething, M.-J., and Sambrook, J., Protein folding in the cell. Nature355 (1992) 33–45.PubMedGoogle Scholar
  30. 30.
    Haas, I. G., BiP — a heat shock protein involved in immunoglobulin chain assembly. Curr. Topics Microbiol. Immun.167 (1991) 71–82.Google Scholar
  31. 31.
    Haas, I. G., and Meo, T., cDNA cloning of the immunoglobulin heavy chain binding protein. Proc. natl. Acad. Sci. USA85 (1988) 2250–4.PubMedGoogle Scholar
  32. 32.
    Haas, I. G., and Wabl, M., Immunoglobulin heavy chain binding protein. Nature306 (1983) 387–389.PubMedGoogle Scholar
  33. 33.
    Hammond, C., Braakman, I., and Helenius, A., Role of N-linked oligosaccharide recognition, glucose triming, and calnexin in glycoprotein folding and quality control. Proc. natl Acad. Sci. USA91 (1994) 913–917.PubMedGoogle Scholar
  34. 34.
    Hendershot, L. M., Bole, D., Köhler, G., and Kearney, J. F., Assembly and secretion of heavy chains that do not associate posttranslationally with immunoglobulin heavy chain binding protein. J. Cell Biol.104 (1987) 761–767.PubMedGoogle Scholar
  35. 35.
    Hendershot, L. M., Ting, J., and Lee, A. S., Identity of the immunoglobulin heavy chain binding protein with the 78,000 dalton glucose-regulated protein and the role of post-translational modifications in its binding function. Molec. cell. Biol.8 (1988) 4250–4256.PubMedGoogle Scholar
  36. 36.
    Hendrick, J. P., and Hartl, F.-U., Molecular chaperone functions of heat-shock proteins. A. Rev. Biochem.62 (1993) 349–384.Google Scholar
  37. 37.
    Hou, M. C., Shen, C. H., Lee, W. C., and Lai, Y. K., Okadaic acid as an inducer of the 78-kDa glucose-regulated protein in 9L rat brain tumor cells. J. cell. Biochem.51 (1993) 91–101.PubMedGoogle Scholar
  38. 38.
    Hurtley, S. M., Bole, D. G., Hoover, L. H., Helenius, A., and Copeland, C. S., Interactions of misfolded influenza virus hemagglutinin with binding protein (BiP). J. Cell Biol.108 (1989) 2117–26.PubMedGoogle Scholar
  39. 39.
    Kabsch, W., Mannherz, H. G., Suck, D., Pai, E. F., and Holmes, K. E., Atomic structure of the actin: DNase I complex. Nature437 (1990) 37–44.Google Scholar
  40. 40.
    Kassenbrock, C. K., and Kelly, R. B., Interaction of heavy chain binding protein (BiP/GRP78) with adenine nucleotides. EMBO J.8 (1989) 1461–7.PubMedGoogle Scholar
  41. 41.
    Kim, P. S., and Arvan, P., Hormonal regulations of thyroglobulin export from the endoplasmic reticulum of cultured thyrocytes. J. biol. Chem.268 (1993) 4873–9.PubMedGoogle Scholar
  42. 42.
    Kim, P. S., Bole, D., and Arvan, P., Transient aggregation of nascent thyroglobulin in the endoplasmic reticulum: relationship to the molecular chaperone, BiP. J. Cell Biol.118 (1992) 541–9.PubMedGoogle Scholar
  43. 43.
    Knittler M. R., and Haas, I. G., Interaction of BiP with newly synthesized immunoglobulin light chain molecules: cycles of sequential binding and release. EMBO J.11 (1992) 1573–81.PubMedGoogle Scholar
  44. 43a.
    Knittler, M. R., Dirks, S., and Haas, I. G., Molecular chaperones involved in ER-degradation: quantitative BiP-interaction of partially folded Ig L chains that are degraded in the ER. Proc. natl Acad. Sci. USA (1994) in press.Google Scholar
  45. 44.
    Kozutsumi, Y., Segal, M., Normington, K., Gething, M. J., and Sambrook, J., The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature332 (1988) 462–4.PubMedGoogle Scholar
  46. 45.
    Landry, S. J., Jordan, R., McMacken, R., and Gierasch, L. M., Different conformations for the same polypeptide bound to chaperones DnaK and GroEL. Nature355 (1992) 455–7.PubMedGoogle Scholar
  47. 46.
    Lee, A. S., Coordinated regulation of a set of genes by glucose and calcium ionophores in mammalian cells. TIBS12 (1987) 20–23.Google Scholar
  48. 47.
    Leno, G. H., and Ledford, B. E., Reversible ADP-ribosylation of the 78 kDa glucose-regulated protein. FEBS Lett.276 (1990) 29–33.PubMedGoogle Scholar
  49. 48.
    Leustek, T., Amir, S. D., Toledo, H., Brot, N., and Weissbach, H., Autophosphorylation of 70 kDa heat shock proteins. Cell. molec. Biol.38 (1992) 1–10.Google Scholar
  50. 49.
    Leustek, T., Toledo, H., Brot, N., and Weissbach, H., Calcium-dependent autophosphorylation of the glucose-regulated protein, Grp78. Archs Biochem. Biophys.289 (1991) 256–61.Google Scholar
  51. 50.
    Lewis, M. J., and Pelham, H. R. B., Involvement of ATP in the nuclear nucleolar functions of the 70kd heat shock protein. EMBO J.4 (1985) 3137–3143.PubMedGoogle Scholar
  52. 51.
    Lewis, M. J., and Pelham, H. R. B., Ligand-induced redistribution of a human KDEL receptor from the Golgi complex to the endoplasmic reticulum. Cell68 (1992) 353–364.PubMedGoogle Scholar
  53. 52.
    Lewis, M. J., Sweet, D. J., and Pelham, H. R. B., The ERD2 gene determines the specificity of the luminal ER protein retention system. Cell61 (1990) 1359–63.PubMedGoogle Scholar
  54. 53.
    Li, X. A., and Lee, A. S., Competitive inhibition of a set of endoplasmic reticulum protein genes (GRP78, GRP94, and ERp72) retards cell growth and lowers viability after ionophore treatment. Molec. cell. Biol.11 (1991) 3446–53.PubMedGoogle Scholar
  55. 54.
    Lin, H.-Y., Masso-Welch, P., Di, Y.-P., Cai, J.-W., Shen, J.-W., and Subjeck, J. R., The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein that binds immunoglobulin. Molec. Biol. Cell4 (1993) 1109–1119.PubMedGoogle Scholar
  56. 55.
    Lindquist, S., and Craig, E. A., The heat-shock proteins. A. Rev. Genet.22 (1988) 631–677.Google Scholar
  57. 56.
    Lodish, H. F., and Kong, N., The secretory pathway is normal in dithiothreitol-treated cells, but disulfide-bonded proteins are reduced and reversibly retained in the endoplasmic reticulum. J. biol. Chem.268 (1993) 20598–20605.PubMedGoogle Scholar
  58. 57.
    Ma, J., Kearney, J. F., and Hendershot, L. M., Association of transport-defective light chains with immunoglobulin heavy chain binding protein. Molec. Immun.27 (1990) 623–30.PubMedGoogle Scholar
  59. 58.
    Machamer, C. E., Doms, R. W., Bole, D. G., Helenius, A., and Rose, J. K., Heavy chain binding protein recognizes incompletely disulfide-bonded forms of vesicular stomatitis virus G protein. J. biol. Chem265 (1990) 6879–83.PubMedGoogle Scholar
  60. 59.
    McCarty, J. S., and Walker, G. C., DnaK as a thermometer: threonine-199 is site of autophosphorylation and is critical for ATPase activity. Proc. natl Acad. Sci. USA88 (1991) 9513–7.PubMedGoogle Scholar
  61. 60.
    Melnick, J., Aviel, S., and Argon, Y., The endoplasmic reticulum stress protein GRP94, in addition to BiP, associates with unassembled immunoglobulin chains. J. biol. Chem.267 (1992) 21303–6.PubMedGoogle Scholar
  62. 61.
    Mizzen, L. A., Kabiling, A. K., and Welch, W. J., The two mammalian mitochondrial stress proteins, grp 75 and hsp 58, transiently interact with newly synthesized mitochondrial proteins. Cell Regul.2 (1991) 165–173.PubMedGoogle Scholar
  63. 62.
    Mori, K., Ma, W., Gething, M. J., and Sambrook, J., A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell74 (1993) 743–56.PubMedGoogle Scholar
  64. 63.
    Mori, K., Sant, A., Kohno, K., Normington, K., Gething, M. J., and Sambrook, J. F., A 22 bp cis-acting element is necessary and sufficient for the induction of the yeast KAR2 (BiP) gene by unfolded proteins. EMBO J.11 (1992) 2583–93.PubMedGoogle Scholar
  65. 64.
    Munro, S., and Pelham, H. R. B., An Hsp 70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell46 (1986) 291–300.PubMedGoogle Scholar
  66. 65.
    Munro, S., and Pelham, H. R. B., A C-terminal signal prevents secretion of luminal ER proteins. Cell48 (1987) 899–907.PubMedGoogle Scholar
  67. 66.
    Ng, D. T., Hiebert, S. W., and Lamb, R. A., Different roles of individual N-linked oligosaccharide chains in folding, assembly, and transport of the simian virus 5 hemagglutinin-neuraminidase. Molec. cell. Biol.10 (1990) 1989–2001.PubMedGoogle Scholar
  68. 67.
    Ng, D. T., Randall, R. E., and Lamb, R. A., Intracellular maturation and transport of the SV5 type II glycoprotein hemagglutinin-neuraminidase: specific and transient association with GRP78-BiP in the endoplasmic reticulum and extensive internalization from the cell surface. J. Cell Biol.109, (1989) 3273–89.PubMedGoogle Scholar
  69. 68.
    Ng, D. T., Watowich, S. S., and Lamb, R. A., Analysis in vivo of GRP78-BiP/substrate interactions and their role in induction of the GRP78-BiP gene. Molec. Biol. Cell3 (1992) 143–55.PubMedGoogle Scholar
  70. 69.
    Nguyen, T. H., Law, D. T., and Williams, D. B., Binding protein BiP is required for translocation of secretory proteins into the endoplasmic reticulum in Saccharomyces cerevisiae. Proc. natl Acad. Sci. USA88 (1991) 1565–9.PubMedGoogle Scholar
  71. 70.
    Nicchitta, C. V., and Blobel, G., Luminal proteins of the mammalian endoplasmic reticulum are required to complete protein translocation. Cell73 (1993) 989–998.PubMedGoogle Scholar
  72. 71.
    Nicholson, R. C., Williams, D. B., and Moran, L. A., An essential member of the HSP70 gene family of Saccharomyces cerevisiae is homologous to immunoglobulin heavy chain binding protein. Proc. natl Acad. Sci. USA87 (1990) 1159–63.PubMedGoogle Scholar
  73. 72.
    Nikawa, J. I., and Yamashita, S.,IRE1 encodes a putative protein kinase containing a membrane-spanning domain and is required for inositol phototrophy inSaccharomyces cerevisiae. Molec. Microbiol.6 (1992) 1441–1446.Google Scholar
  74. 73.
    Normington, K., Kohno, K., Kozutsumi, Y., Gething, M. J., and Sambrook, J., S. cerevisiae encodes an essential protein homologous in sequence and function to mammalian BiP. Cell57 (1989) 1223–36.PubMedGoogle Scholar
  75. 74.
    Otterson, G. A., Flynn, G. C., Kratzke, R. A., Coxon, A., Johnston, P. G., and Kaye, F. J., Stch encodes the ‘ATPase’ core of a microsomal stress 70 protein. EMBO J.13 (1994) 1216–1225.PubMedGoogle Scholar
  76. 75.
    Pelham, H. R. B., Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell46 (1986) 959–961.PubMedGoogle Scholar
  77. 76.
    Peluso, R. W., Lamb, R. A., and Choppin, P. W., Infection with paramyxoviruses stimulates synthesis of cellular polypeptides that are also stimulated in cells transformed by Rous sarcoma virus or deprived of glucose. Proc. natl Acad. Sci. USA75 (1978) 6120–6124.PubMedGoogle Scholar
  78. 77.
    Rippmann, F., Taylor, W. R., Rothbard, J. B., and Green, N. M., A hypothetical model for the peptide binding domain of hsp70 based on the peptide binding domain of HLA. EMBO J.10 (1991) 1053–9.PubMedGoogle Scholar
  79. 78.
    Rose, M. D., Misra, L. M., and Vogel, J. P., KAR2, a karyogamy gene, is the yeast homolog of the mammalian BiP/GRP78 gene [published erratum appears in Cell 1989 Aug 25; 58 (4): following 801]. Cell57 (1989) 1211–21.PubMedGoogle Scholar
  80. 79.
    Rothman, J. E., Polypeptide chain binding proteins: catalysts of protein folding and related processes in cells. Cell59 (1989) 591–601.PubMedGoogle Scholar
  81. 80.
    Sanders, S. L., Whitfield, K. M., Vogel, J. P., Rose, M. D., and Schekman, R. W., Sec61p and BiP directly facilitate polypeptide translocation into the ER. Cell69 (1992) 353–65.PubMedGoogle Scholar
  82. 81.
    Satoh, M., Nakai, A., Sokawa, Y., Hirayoshi, K., and Nagata, K., Modulation of the phosphorylation of glucose-regulated protein, GRP78, by transformation and inhibition of glycosylation. Expl Cell Res.205 (1993) 76–83.Google Scholar
  83. 82.
    Schroder, H., Langer, T., Hartl, F. U., and Bakau, D., DnaK, DnaJ and GrpE form a cellular chaperone machinery capable of repairing heat-induced protein damage. EMBO J.12 (1993) 4137–44.PubMedGoogle Scholar
  84. 83.
    Silver, P. A., and Way, J. C., Eukaryotic DnaJ homologs and the specificity of Hsp70 activity. Cell74 (1993) 5–6.PubMedGoogle Scholar
  85. 84.
    Staddon, J. M., Bouzyk, M. M., and Rozengurt, E., Interconversion of GRP78/BiP. A novel event in the action of Pasteurella multocida toxin, bombesin, and platelet-derived growth factor. J. biol. Chem.267 (1992) 25239–45.PubMedGoogle Scholar
  86. 85.
    Vogel, J. P., Misra, L. M., and Rose, M. D., Loss of BiP/GRP78 function blocks translocation of secretory proteins in yeast. J. Cell Biol.110 (1990) 1885–95.PubMedGoogle Scholar
  87. 86.
    Wall, D., Zylicz, M., and Georgopoulos, C., The NH2-terminal 108 amino acids of theEscherichia coli DnaJ protein stimulate the ATPase activity of DnaK and are sufficient for λ-replication. J. biol. Chem.269 (1994) 5446–5451.PubMedGoogle Scholar
  88. 87.
    Watowich, S. S., Morimoto, R. I., and Lamb, R. A., Flux of the paramyxovirus hemagglutinin-neuraminidase glycoprotein through the endoplasmic reticulum activates transcription of the GRP78-BiP gene. J. Virol.65 (1991) 3590–7.PubMedGoogle Scholar
  89. 88.
    Weitz, G., and Proia, R. L., Analysis of the glycosylation and phosphorylation of the alpha-subunit of the lysosomal enzyme, beta-hexosaminidase A, by site-directed mutagenesis. J. biol. Chem.267 (1992) 10039–44.PubMedGoogle Scholar
  90. 89.
    Welch, W., Garrels, J. I., Thomas, G. P., Lin, J. J.-C., and Feramisco, J. R., Biochemical characterization of the mammalian stress proteins and identification of two stress proteins as glucose- and Ca2+-ionophore-regulated proteins. J. biol. Chem.258 (1983) 7102–7111.PubMedGoogle Scholar
  91. 90.
    Welch, W. J., and Feramisco, J. R., Rapid purification of mammalian 70.000-dalton stress proteins: affinity of the proteins for nucleotides. Molec. Cell Biol.5 (1985) 1229–1237.PubMedGoogle Scholar
  92. 91.
    Williams, A. M., and Enns, C. A., A region of the C-terminal portion of the human transferrin receptor contains an asparagine-linked glycosylation site critical for receptor structure and function. J. biol. Chem.268 (1993) 12780–6.PubMedGoogle Scholar
  93. 92.
    Zhang, Y., and Dahms, N. M., Site-directed removal of N-glycosylation sites in the bovine cation-dependent mannose-6-phosphate receptor: effects on ligand binding, intracellular targetting and association with binding immunoglobulin protein. Biochem. J.295 (1993) 841–848.PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel 1994

Authors and Affiliations

  • I. G. Haas
    • 1
  1. 1.Institut für Biochemie der Universität HeidelbergHeidelberg(Germany)

Personalised recommendations