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Complete protein sequence and identification of structural domains of human apolipoprotein B

Nature volume 323, pages 734–738 (1986)Cite this article

Abstract

Epidemiological, pathological and genetic studies show a strong positive correlation between elevated plasma concentrations of low-density lipoprotein (LDL) cholesterol and the risk of premature coronary heart disease1–3. Apolipoprotein (apo) B-100 is the sole protein component of LDL and is the ligand responsible for the receptor-mediated uptake and clearance of LDL from the circulation2–6. Apo B-100 is made by the liver and is essential for the assembly of triglyceride-rich very low-density lipoproteins (VLDL) in the cisternae of the endoplasmic reticulum and for their secretion into the plasma. VLDL transports triglyceride to peripheral muscle and adipose tissue, where the triglyceride is hydrolysed by lipoprotein lipase. The resultant particle, relatively enriched in cholesteryl ester, constitutes LDL. LDL delivers cholesterol to peripheral tissues where it is used for membrane and steroid hormone biosynthesis and to the liver, the only organ which can catabolize and excrete cholesterol. Plasma LDL levels are therefore determined by the balance between their rate of production from VLDL and clearance by the hepatic LDL (apo B/E) receptor pathway. Here we report the complete 4,563-amino-acid sequence of apo B-100 precursor (relative molecular mass (Mr) 514,000 (514K)) determined from complementary DNA clones. Numerous lipid-binding structures are distributed throughout the extraordinary length of apo B-100 and must underlie its special functions as a nucleus for lipoprotein assembly and maintenance of plasma lipoprotein integrity. A domain enriched in basic amino-acid residues has been identified as important for the cellular uptake of cholesterol by the LDL receptor pathway.

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References

  1. LaRosa, J. C., Glueck, C. J. & Segal, M. D. Circulation 73, 1–133 (1986).

    Article  Google Scholar 

  2. Havel, R. J., Goldstein, J. L. & Brown, M. S. in Metabolic Control and Disease (eds Bondy, P. K. & Rosenberg, L. E.) 393–494 (Saunders, Philadelphia, 1980).

    Google Scholar 

  3. Goldstein, J. L. & Brown, M. S. in The Metabolic Basis of Inherited Disease (eds Stanbury, J. B. et al.) 672–712 (McGraw-Hill, New York, 1983).

    Google Scholar 

  4. Mahley, R. W., Innerarity, T. L., Rall, S. C. & Weisgraber, K. H. J. Lipid Res. 25, 1277–1294 (1984).

    CAS  PubMed  Google Scholar 

  5. Kane, J. P. A. Rev. Physiol. 45, 637–650 (1983).

    Article  CAS  Google Scholar 

  6. Breslow, J. L. A. Rev. Biochem. 54, 699–727 (1985).

    Article  CAS  Google Scholar 

  7. Knott, T. J. et al. Nucleic Acids Res. 13, no. 18 (1986).

  8. Cardin, A. D. et al. J. biol. Chem. 239, 8522–8528 (1984).

    Google Scholar 

  9. Lee, P. & Breckenridge, W. C. Can. J. Biochem. 54, 42–49 (1976).

    Article  CAS  Google Scholar 

  10. Chou, P. Y. & Fasman, G. D. A. Rev. Biochem. 47, 251–276 (1978).

    Article  CAS  Google Scholar 

  11. Cardin, A. D., Witt, K. R., Barnhart, C. L. & Jackson, R. L. Biochemistry 21, 4503–4511 (1982).

    Article  CAS  Google Scholar 

  12. Segrest, J. P., Jackson, R. L., Morrisett, J. D. & Gotto, A. M. FEBS Lett. 38, 347–353 (1974).

    Article  Google Scholar 

  13. Kaiser, E. T. & Kezdy, F. J. Science 223, 249–255 (1984).

    Article  ADS  CAS  Google Scholar 

  14. Osterman, D., Mora, R., Kezdy, F. J., Kaiser, E. T. & Meredith, S. C. J. Am. chem. Soc. 106, 6845–6847 (1984).

    Article  CAS  Google Scholar 

  15. Kyte, J. & Doolittle, R. F. J. molec. Biol. 157, 105–132 (1982).

    Article  CAS  Google Scholar 

  16. Van't Hooft, F. & Havel, R. J. J. biol. Chem. 256, 3963–3968 (1981).

    CAS  PubMed  Google Scholar 

  17. Südhof, T. C. et al. Science 228, 893–895 (1985).

    Article  ADS  Google Scholar 

  18. Doolittle, R. F. Trends biochem. Sci. 10, 233–237 (1985).

    Article  CAS  Google Scholar 

  19. Freedman, R. B. Trends biochem. Sci. 9, 438–441 (1984).

    Article  CAS  Google Scholar 

  20. Edman, J. C., Ellis, L., Blacher, R. W., Roth, R. A. & Rutter, W. J. Nature 317, 267–270 (1985).

    Article  ADS  CAS  Google Scholar 

  21. Yamamoto, T., Bishop, R. W., Brown, M. S., Goldstein, J. L. & Russell, D. W. Science 232, 1230–1237 (1986).

    Article  ADS  CAS  Google Scholar 

  22. Christensen, N. J., Rubin, C. E., Cheung, M. C. & Albers, J. J. J. Lipid Res. 24, 1229–1242 (1983).

    CAS  PubMed  Google Scholar 

  23. Vauhkonen, M., Vitala, J., Parkkinen, J. & Rauvala, H. Eur. J. Biochem. 152, 43–50 (1985).

    Article  CAS  Google Scholar 

  24. Siuta-Mangano, P., Janero, D. R. & Lane, M. D. J. biol. Chem. 257, 11463–11467 (1982).

    CAS  PubMed  Google Scholar 

  25. Eisenberg, S. & Levy, R. I. Adv. Lipid Res. 13, 1–89 (1975).

    Article  CAS  Google Scholar 

  26. Teng, B. et al. J. biol. Chem. 260, 5067–5072 (1985).

    CAS  PubMed  Google Scholar 

  27. Innerarity, T. L., Friedlander, E. J., Rall, S. C., Weisgraber, K. H. & Mahley, R. W. J. biol. Chem. 258, 12341–12347 (1983).

    CAS  PubMed  Google Scholar 

  28. Weisgraber, K. H. et al. J. biol. Chem. 258, 12348–12354 (1983).

    CAS  PubMed  Google Scholar 

  29. Innerarity, T. L. et al. J. biol. Chem. 259, 7261–7267 (1984).

    CAS  PubMed  Google Scholar 

  30. Knott, T. J. et al. Science 230, 37–43 (1985).

    Article  ADS  CAS  Google Scholar 

  31. Elovson, J., Jacobs, J. C., Schumaker, V. N. & Puppione, D. L. Biochemistry 24, 1569–1578 (1985).

    Article  CAS  Google Scholar 

  32. Deckelbaum, R. J., Shipley, G. G. & Small, D. M. J. biol. Chem. 252, 744–754 (1977).

    CAS  PubMed  Google Scholar 

  33. Berg, K. & Bearn, A. B. Clin. Genet. 1, 104–120 (1970).

    Article  Google Scholar 

  34. Rapasz, M. & Hasler-Rapasz, J. Fedn Proc. 72, 2347–2351 (1985).

    Google Scholar 

  35. Young, S. G., Bertics, S. J., Curtiss, L. K., Casal, D. C. & Witztum, J. L. Proc. natn. Acad. Sci. U.S.A. 83, 1101–1105 (1986).

    Article  ADS  CAS  Google Scholar 

  36. Berg, K. et al. Proc. natn. Acad. Sci. U.S.A. (in the press).

  37. Hardman, D. A., Gustafson, A., Schilling, J. W., Donaldson, V. H. & Kane, J. P. Biochem. biophys. Res. Commun. 137, 821–825 (1986).

    Article  CAS  Google Scholar 

  38. LeBoeuf, R. C. et al. FEBS Lett. 170, 105–108 (1984).

    Article  CAS  Google Scholar 

  39. Belt, K. I., Carroll, M. C. & Porter, R. R. Cell 36, 907–914 (1984).

    Article  CAS  Google Scholar 

  40. Kane, J. P., Hardman, D. A. & Paulus, H. E. Proc. natn. Acad. Sci. U.S.A. 77, 2465–2469 (1980).

    Article  ADS  CAS  Google Scholar 

  41. Eisenberg, D., Schwarz, E., Komaromy, M. & Wall, R. J. molec. Biol. 179, 125–142 (1984).

    Article  CAS  Google Scholar 

  42. Marcel, Y. L., Hogue, M., Theolis, R. & Milne, R. W. J. biol. Chem. 257, 13165–13168 (1982).

    CAS  PubMed  Google Scholar 

  43. Young, S. G., Witztum, J. L., Casal, D. C., Curtiss, L. K. & Bernstein, S. Arteriosclerosis 6, 178–188 (1986).

    Article  CAS  Google Scholar 

  44. Ruther, U. & Müller-Hill, B. EMBO J. 2, 1791–1794 (1983).

    Article  CAS  Google Scholar 

  45. Johnston, S., Lee, J. H. & Ray, D. S. Gene 34, 137–145 (1985).

    Article  CAS  Google Scholar 

  46. Burnette, W. N. Analyt. Biochem. 112, 195–203 (1981).

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Molecular Medicine Research Group, MRC Clinical Research Centre, Watford Road, Harrow, HA1 3UJ, UK

    T. J. Knott, R. J. Pease, L. M. Powell, S. C. Wallis & J. Scott

  2. Gladstone Foundation Laboratories, Cardiovascular Research Institute, Departments of Medicine, Pathology and Pharmaceutical Chemistry, University of California, San Francisco, California, 94140, USA

    S. C. Rall Jr, T. L. Innerarity, B. Blackhart, B. J. McCarthy, R. W. Mahley & B. Levy-Wilson

  3. Department of Crystallography, Birkbeck College, University of London, London, WC1E 7HX, UK

    W. H. Taylor

  4. Clinical Research Institute of Montreal, 110 West Pine Avenue, Montreal, Quebec, H2W 1R7, Canada

    Y. Marcel & R. Milne

  5. Department of Medicine, University of California, Los Angeles, California, 90024, USA

    D. Johnson, M. Fuller & A. J. Lusis

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Knott, T., Pease, R., Powell, L. et al. Complete protein sequence and identification of structural domains of human apolipoprotein B. Nature 323, 734–738 (1986). https://doi.org/10.1038/323734a0

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