Bioscience Reports

, Volume 1, Issue 6, pp 461–468 | Cite as

Intramolecular general acid catalysis in the binding reactions of α2 and complement components C3 and C4

  • Stephen G. Davies
  • Robert B. Sim
Article
  • 7 Downloads

Abstract

The complement system proteins C3 and C4 and the plasma protease inhibitor α2-macroglobulin~ when activated by limited proteolysis, can bind covalently to other macromolecules. The three proteins also exhibit an unusual internal peptide-bond cleavage reaction when denatured. The covalent binding reaction is likely to occur by a transacylation mechanism involving an internal thioiester in the three proteins. However, the activated species of these proteins are much more reactive than simple thiolesters. Studies of molecular models of the thiolester region in C3 show that an intramolecular acid catalysis mechanism can both account for the exceptional reactivity of the activated form of these proteins and provide an explanation for the denaturation-induced peptide bond cleavage.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lachmann PJ (1979) inThe Antigens vol. 5, (Sela M, ed), 284–354, Academic Press, London.Google Scholar
  2. 2.
    Müller-Eberhard HJ (1980) inProgress in Immunology IV (Fougereau M & Dausset J, eds), 1001–1024, Academic Press, London.Google Scholar
  3. 3.
    Law SK & Levine RP (1977) Proc. Natl. Acad. Sci. U.S.A.74, 2701–2705.PubMedGoogle Scholar
  4. 4.
    Nussenzweig V (1980) inProgress in Immunology IV (Fougereau M & Dausset J, eds), 1044–1056, Academic Press, London.Google Scholar
  5. 5.
    Law SK, Lichtenberg NA & Levine RP (1980) J. Immunol.123, 1388–1394.Google Scholar
  6. 6.
    Campbell RD, Dodds AW & Porter RR (1980) Biochem. J.189, 67–80.PubMedGoogle Scholar
  7. 7.
    Gadd KJ & Reid KBM (1981) Biochem. J.195, 471–480.PubMedGoogle Scholar
  8. 8.
    Sim RB, Twose TM, Paterson DS & Sim E (1981) Biochem. J.193, 115–127.PubMedGoogle Scholar
  9. 9.
    Salvesen GS & Barrett AJ (1980) Biochem. J.187, 695–701.PubMedGoogle Scholar
  10. 10.
    Sim RB & Sim E (1981) Biochem J.193, 129–141.PubMedGoogle Scholar
  11. 11.
    Tack BF, Harrison RA, Janatova J, Thomas ML & Prahl JW (1980) Proc. Natl. Acad. Sci. U.S.A.77, 5764–5768.PubMedGoogle Scholar
  12. 12.
    Swenson RP & Howard JB (1980) J. Biol. Chem.255, 8087–8091.PubMedGoogle Scholar
  13. 13.
    Sottrup-Jensen L, Petersen TE & Magnusson S (1980) FEBS Lett.121, 275–279.PubMedGoogle Scholar
  14. 14.
    von Zabern I, Nolte R & Vogt W (1981) Scand. J. Immunol., in press.Google Scholar
  15. 15.
    Lundwall Å, Malmheden I, Hellman U & Sjoquist J (1981) Scand. J. Immunol.13, 199–203.PubMedGoogle Scholar
  16. 16.
    Swenson RP & Howard JB (1979) Proc. Natl. Acad. Sci. U.S.A.76, 4313–4316.PubMedGoogle Scholar
  17. 17.
    Barrett AJ, Brown MA & Sayers CA (1979) Biochem. J.181, 401–418.PubMedGoogle Scholar
  18. 18.
    Fedor LR & Bruice TC (1964) J. Amer. Chem. Soc.86, 4117–4123.Google Scholar
  19. 19.
    Fedor LR & Bruice TC (1964) J. Amer. Chem. Soc.86, 4886–4897.Google Scholar
  20. 20.
    Vagelos PR & Earl JM (1959) J. Biol. Chem.234, 2272–2280.PubMedGoogle Scholar
  21. 21.
    Twose TM, Sim RB & Paterson DS (1980) Abstr. 4th Int. Congr. Immunol. Abstr, no. 15.1.22, Paris, July.Google Scholar
  22. 22.
    Salvesen GS, Sayers CA & Barrett AJ (1981) Biochem. J.195, 453–461.PubMedGoogle Scholar
  23. 23.
    Janatova J, Lorenz PE, Schechter AN, Prahl JW & Tack BF (1980) Biochemistry19, 4471–4478.PubMedGoogle Scholar
  24. 24.
    Jencks WP (1972) Chem. Rev.72, 705–725.Google Scholar
  25. 25.
    Stewart R & Srinavasan R (1978) Acc. Chem. Res.11, 271–275.Google Scholar
  26. 26.
    Hugli TE (1975) J. Biol. Chem.250, 8293–8301.PubMedGoogle Scholar
  27. 27.
    Tack BF, Morris SC & Prahl JW (1979) Biochemistry18, 1497–1503.PubMedGoogle Scholar
  28. 28.
    Sotrup-Jensen L, Stepanik TM, Jones CM, Petersen TE & Magnusson S (1979) inPhysiological Inhibitors of Coagulation and Fibrinolysis (Collen D, Wiman B & Verstraete M, eds), 255–271, Elsevier, Amsterdam.Google Scholar

Copyright information

© The Biochemical Society 1981

Authors and Affiliations

  • Stephen G. Davies
    • 1
  • Robert B. Sim
    • 2
  1. 1.The Dyson Perrins LaboratoryOxfordUK
  2. 2.MRC Immunochemistry Unit, Department of BiochemistryUniversity of OxfordOxfordUK

Personalised recommendations