Skip to main content
SpringerLink
Log in

Structure-function relationships in insulin

  • Published:
Bioscience Reports

Abstract

A new interpretation of structure-function relationships in the insulin molecule is presented. Negative cooperativity is postulated to arise from a dimerization event occurring between two receptor-bound molecules. The receptor-binding surface of insulin can necessarily not involve residues involved in dimerization as has been generally accepted. Support for this interpretation is based on published data.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. De Meyts P, Roth J, Neville DM Jr, Gavin JR III & Lesniak MA (1973) Biochem. Biophys. Res. Commun.55, 154–161.

    PubMed  Google Scholar 

  2. De Meyts P, Bianco AR & Roth J (1976) J. Biol. Chem.251, 1877–1888.

    PubMed  Google Scholar 

  3. Ginsberg BH, Kahn CR & Roth J (1976) Biochim. Biophys. Acta443, 227–242.

    PubMed  Google Scholar 

  4. De Meyts P (1976) inHormones and Cell Regulation, vol4 (Dumont J & Nunez J, eds), pp 107–121, Elsevier/North Holland Biomedical Press.

  5. Pollet RJ, Standaert ML & Haase BS (1977) J. Biol. Chem.252, 5828–5834.

    PubMed  Google Scholar 

  6. De Lean A & Rodbard D (1979) inThe Receptors, vol 1 (O'Brien RD, ed), pp 143–192, Plenum Press.

  7. De Meyts P, Van Obberghen E, Roth J, Wollmer A & Brandenburg D (1978) Nature (London)273, 504–509.

    Google Scholar 

  8. Pullen RA, Lindsay DA, Wood SP, Tickle IJ, Blundell TL, Wollmer A, Krail G, Brandenburg D, Zahn H, Gliemann J & Gammeltoft S (1976) Nature (London)259, 369–373.

    Google Scholar 

  9. Blundell TL, Dodson GG, Hodgkin DC & Mercola DA (1972) Adv. Prot. Chem.26, 279–402.

    Google Scholar 

  10. Cuatrecasas P & Hollenberg MD (1975) Biochem. Biophys. Res. Commun.62, 31–41.

    PubMed  Google Scholar 

  11. Jacobs S, Shechter Y, Bissell K, & Cuatrecasas P (1977) Biochem. Biophys. Res. Commun.77, 981–988.

    PubMed  Google Scholar 

  12. Yip CC, Yeung CWT & Moule ML (1978) J. Biol. Chem.253, 1743–1745.

    PubMed  Google Scholar 

  13. Wisher MH, Baron MD, Jones RH, Sönksen PH, Saunders DJ, Thamm P & Brandenburg D (1980) Biochem. Biophys. Res. Commun.92, 492–498.

    PubMed  Google Scholar 

  14. Pilch PF & Czech MP (1979) J. Biol. Chem.254, 3375–3380.

    PubMed  Google Scholar 

  15. Pilch PF & Czech MP (1980) Diabetes29, 945–947.

    PubMed  Google Scholar 

  16. Jacobs S, Hazum E & Cuatrecasas P (1980) J. Biol. Chem.255, 6937–6940.

    PubMed  Google Scholar 

  17. Muggeo M, Ginsberg BH, Roth J, Neville DM, De Meyts P & Kahn CR (1979) Endocrinology104, 1393–1402.

    PubMed  Google Scholar 

  18. Klingenberg M (1981) Nature (London)290, 449–453.

    Google Scholar 

  19. Kahn CR & Baird K (1979) J. Biol. Chem.253, 4900–4906.

    Google Scholar 

  20. Donner DB & Corin RE (1980) J. Biol. Chem.255, 9005–9008.

    PubMed  Google Scholar 

  21. Gammeltoft S, Kristensen LO & Sestoft L (1978) J. Biol. Chem.253, 8406–8413.

    PubMed  Google Scholar 

  22. Kahn CR, Baird KL, Jarrett DB & Flier JS (1978) Proc. Natl. Acad. Sci. U.S.A.75, 4209–4213.

    PubMed  Google Scholar 

  23. Shechter Y, Chang KJ, Jacobs S & Cuatrecasas P (1979) Proc. Natl. Acad. Sci. U.S.A.76, 2720–2724.

    PubMed  Google Scholar 

  24. Ketelslegers JM, Maghuin-Rogister G, Pirens G & Hennen G (1979) XIth Internat. Biochemistry Congress, Toronto, Abstracts, p 604.

  25. Boesel RW & Carpenter FH (1972) Fed. Proc.31, 255.

    Google Scholar 

  26. Wood SP, Blundell TL, Wollmer A, Lazarus NR & Neville RWJ (1975) Eur. J. Biochem.55, 531–542.

    PubMed  Google Scholar 

  27. Horuk R, Blundell TL, Lazarus NR, Neville RWJ, Stone D & Wollmer A (1980) Nature (London)285, 822–824.

    Google Scholar 

  28. Weber G (1975) Advances Prot. Chem.29, 1–83.

    Google Scholar 

  29. Goldman J & Carpenter FH (1974) Biochemistry13, 4566–4574.

    PubMed  Google Scholar 

  30. Piron M, Michiels-Place M, Waelbroek M, De Meyts P, Schüttler A & Brandenburg D (1980) inInsulin, Proceedings of the 2nd International Insulin Symposium, Aachen (Brandenburg D & Wollmer A, eds), pp 371–392.

  31. Willey KP, Tatnell MA, Jones RH, Schüttler A & Brandenburg D (1980) inInsulin, Proceedings of the 2nd International Insulin Symposium, Aachen (Brandenburg D & Wollmer A, eds), pp 425–432.

  32. Pitts J (1980) inProceedings of the 10th Congress of the I.D.F., Vienna (Waldhäusl WK, ed), pp 88–91, Excerpta Medica.

  33. Kikuchi K, Larner J, Freer RJ, Day AR, Morris H & Dell A (1980) J. Biol. Chem.255, 9281–9288.

    PubMed  Google Scholar 

  34. Brandenburg D, Gattner H-G & Wollmer A (1972) Hoppe-Seyler's Z. Physiol. Chem.353, 599–617.

    PubMed  Google Scholar 

  35. Wieneke H-J, Danho W, Büllesbach E, Gattner H-G & Zahn H inProceedings of the 6th Amer. Peptide Symposium, Washington DC, June 1979 (Gross E & Meienhofer J, eds), pp. 515–518, Pierce Chem. Co., Rockford, Illinois.

    Google Scholar 

  36. Citti K, Battini L, Cechetti P & Navalesi R (1977) J. Nuc. Med. and Allied Sciences21, 152–158.

    Google Scholar 

  37. Danho W, Sasaki A, Büllesbach E, Föhles J & Gattner H-G (1980) Hoppe-Seyler's Z. Physiol. Chem.361, 735–746.

    PubMed  Google Scholar 

  38. Sodoyez JC, Sodoyez-Goffaux F, Goff MM, Zimmerman AE & Arquilla ER (1975) J. Biol. Chem.250, 4268.

    PubMed  Google Scholar 

  39. Gliemann J, Sonne O, Linde S & Hansen B (1979) Biochem. Biophys. Res. Commun.87, 1183–1190.

    PubMed  Google Scholar 

  40. Danho W, Sasaki A, Büllesbach E, Gattner H-G & Wollmer A (1980) Hoppe-Seyler's Z. Physiol. Chem.361, 747–754.

    PubMed  Google Scholar 

  41. Brandenburg D, Biela M, Herbertz L, & Zahn H (1975) Hoppe-Seyler's Z. Physiol. Chem.356, 961–979.

    PubMed  Google Scholar 

  42. Saunders DJ (1974) D. Phil. thesis, Oxford.

  43. Märki F, De Gasparo M, Eisele K, Kamber B, Riniker B, Rittel W & Sieber P (1979) Hoppe-Seyler's Z. Physiol. Chem.360, 1619–1632.

    PubMed  Google Scholar 

  44. Geiger R, Geisen K, Summ H-D & Langner D (1975) Hoppe-Seyler's Z. Physiol. Chem.356, 1635–1649.

    PubMed  Google Scholar 

  45. Geiger R, Geisen K, Regitz G, Summ H-D & Langner D (1980) Hoppe-Seyler's Z. Physiol. Chem.361, 563–570.

    PubMed  Google Scholar 

  46. Saunders DJ & Offord RE (1977) Hoppe-Seyler's Z. Physiol. Chem.358, 1469–1474.

    PubMed  Google Scholar 

  47. Brandenburg D & Wollmer A (1973) Hoppe-Seyler's Z. Physiol. Chem.354, 613–627.

    PubMed  Google Scholar 

  48. Dodson EJ, Dodson GG, Hodgkin D & Reynolds CD (1979) Can. J. Biochem.57, 469–479.

    PubMed  Google Scholar 

  49. Saunders DJ, unpublished observations.

  50. Carpenter FH (1966) Amer. J. Med.40, 750.

    PubMed  Google Scholar 

  51. Freychet P, Roth J & Neville DM (1971) Proc. Natl. Acad. Sci. U.S.A.68, 1833–1837.

    PubMed  Google Scholar 

  52. Levy D (1973) Biochim. Biophys. Acta13, 153.

    Google Scholar 

  53. Burke GT, Chanley JD, Okada Y, Cosmatos A, Ferderigos N & Katsoyannis PG (1980) Biochemistry19, 4547–4556.

    PubMed  Google Scholar 

  54. Gattner H-G & Schmitt EW (1977) Hoppe-Seyler's Z. Physiol. Chem.358, 105–113.

    PubMed  Google Scholar 

  55. Ferderigos N, Cosmatos A, Ferderigos A & Katsoyannis PG (1979) Int. J. Peptide Protein Res.13, 43–53.

    Google Scholar 

  56. Simon J, Freychet P & Rosselin G (1974) Endocrinology95, 1439–1449.

    PubMed  Google Scholar 

  57. Waelbroek M, Van Obberghen E & De Meyts P (1979) J. Biol. Chem.254, 7736–7740.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Deutsches Wollforschungsinstitut, Veltmanplatz 8, D-5100, Aachen, F.R.G.

    D. J. Saunders

Authors
  1. D. J. Saunders
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saunders, D.J. Structure-function relationships in insulin. Biosci Rep 1, 485–495 (1981). https://doi.org/10.1007/BF01121582

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01121582

Keywords

Search

Navigation