Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Direct evidence for the role of haem doming as the primary event in the cooperative transition of haemoglobin

Abstract

The study of cooperative ligand binding among the four subunits of haemoglobin has played a central role in the understanding of allosteric transitions in a large number of enzymes. Haem iron out-of–plane motion has been suggested to be the trigger for the cooperative transition of haemoglobin. To function as a trigger in a dynamic sense, haem–iron doming must be the first conformational change to occur following ligand dissociation. Here we present the first direct demonstration that haem–iron doming occurs on the same time scale as the breaking of the iron–ligand bond, thus establishing haem–iron doming as the primary event which lead to the R→T transition in haemoglobin.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Perutz, M.F. Mechanisms of cooperativity and allosteric regulation in proteins (Cambridge University Press, Cambridge, 1990).

    Google Scholar 

  2. Monod, J., Wyman, J. & Changeux, J.-P. On the nature of allosteric transitions: a plausible model. J. molec. Biol. 12, 88–118 (1965).

    Article  CAS  PubMed  Google Scholar 

  3. Baldwin, J.M. & Chothia, C. Haemoglobin: the structural changes related to ligand binding and its allosteric mechanism. J. molec. Biol. 129, 175–220 (1979).

    Article  CAS  PubMed  Google Scholar 

  4. Baldwin, J.M. The structure of human carbonmonoxy haemoglobin at 2.7 Å resolution.. J. molec. Biol. 136, 103–128 (1980).

    Article  CAS  PubMed  Google Scholar 

  5. Perutz, M.F. Stereochemistry of cooperative effects in haemoglobin. Nature 228, 726–739 (1970).

    Article  CAS  PubMed  Google Scholar 

  6. Eaton, W.A., Henry, E.R. & Hofrichter, J. Application of linear free energy relations to protein conformational changes: The quaternary structural change of hemoglobin. Proc. natn. Acad. Sci. U.S.A. 88, 4472–4475 (1991).

    Article  CAS  Google Scholar 

  7. Sawicki, C.A. & Gibson, Q.H. Quaternary conformational changes in human hemoglobin studied by laser photolysis of carboxyhemoglobin. J. biol. Chem. 251, 1533–1542 (1976).

    CAS  PubMed  Google Scholar 

  8. Hofrichter, J., Sommer, J.H., Henry, E.R. & Eaton, W.A. Nanosecond absorption spectroscopy of hemoglobin: elementary processes in kinetic cooperativity. Proc. natn. Acad. Sci. U.S.A. 80, 2235–2239 (1983).

    Article  CAS  Google Scholar 

  9. Martin, J.L. et al. Femtosecond photolysis of CO-ligated protoheme and hemoproteins: Appearance of deoxy species with a 350-fsec time constant. Proc. natn. Acad. Sci. U.S.A. 80, 173–177 (1983).

    Article  CAS  Google Scholar 

  10. Lim, M., Jackson, T. A. & Anfinrud, P.A. Nonexponential protein relaxation: dynamics of conformational change in myoglobin. Proc. natn. Acad. Sci. U.S.A. 90, 5801–5804 (1993)

    Article  CAS  Google Scholar 

  11. Findsen, E.W., Friedman, J.M., Ondrias, M.R. & Simon, S.R. Picosecond time-resolved resonance raman studies of hemoglobin: implications for reactivity. Science 229, 661–664 (1985).

    Article  CAS  PubMed  Google Scholar 

  12. Scott, T.W. & Friedman, J.M. Tertiary-structure relaxation in hemoglobin: a transient raman study. J. Am. chem. Soc. 106, 5677–5687 (1984).

    Article  CAS  Google Scholar 

  13. Su, C., Park, Y.D. Liu, G.Y. & Spiro, T.G. Hemoglobin quaternary structure change monitored directly by transient UV resonance Roman spectroscopy. J. Am. chem. Soc. 111, 3457–3459 (1989).

    Article  CAS  Google Scholar 

  14. Olafson, B.D., & Goddard, W.A. Molecular description of dioxygen bonding in hemoglobin. Proc. natn. Acad. Sci. U.S.A. 74, 1315–1319 (1977).

    Article  CAS  Google Scholar 

  15. Henry, E.R., Levitt, M. & Eaton, W.A . Molecular dynamics simulation of photodissociation of carbon monoxide from hemoglobin. Proc. natn. Acad. Sci. U.S.A. 82, 2034–2038 (1985).

    Article  CAS  Google Scholar 

  16. Kuczera, K., Kuriyan, J. & Karplus, M. Temperature dependence of the structure and dynamics of myoglobin: a simulation approach. J. molec. Biol. 213, 351–363 (1990)

    Article  CAS  PubMed  Google Scholar 

  17. Gibson, Q.H., Regan, R., Elber, R., Olson, J.S. & Carver, T.E. Distal pocket residues affect picosecond ligand recombination in myoglobin. J. biol. Chem. 267, 22022–22034 (1992).

    CAS  PubMed  Google Scholar 

  18. Armstrong, R.S., Irwin, M.J. & Wright, P.E. .Soret-excited resonance raman spectrum of (carbonmonoxy) leghemoglobin: assignment of μFe-CO . J. Am. chem. Soc. 104, 626–627 (1982).

    Article  CAS  Google Scholar 

  19. Tsubaki, M., Srivastava, R.B. & Yu, N.-T. Resonance raman investigation of carbon monoxide bonding in (carbonmonoxy)-hemoglobin and -myoglobin: detection of Fe-CO stretching and Fe-C-O bending vibrations and influence of quaternary structure change. Biochemistry 21, 1132–1140 (1982).

    Article  CAS  PubMed  Google Scholar 

  20. Kitagawa, T, Nagai, K. & Tsubaki, M. Assignment of the Fe-Ne (His F8) stretching band in the resonance raman spectra of deoxy myoglobin. FEBS Lett. 104, 376–378 (1979).

    Article  CAS  PubMed  Google Scholar 

  21. Nagai, K. & Kitagawa, T. Differences in Fe(ll)-Ne(His F8) stretching frequencies between deoxyhemoglobins in the two alternative quaternary structures. Proc. natn. Acad. Sci. U.S.A. 77, 2033–2037 (1980).

    Article  CAS  Google Scholar 

  22. Ahmed et al. Evidence for proximal control of ligand specificity in hemeproteins: absorption and Raman studies of cryogenically trapped photoproducts of ligand bound myoglobins. Chem Phys. 158, 329–351 (1991).

    Article  CAS  Google Scholar 

  23. Petrich, J.W., Poyart, C. & Martin, J.L. Photophysics and reactivity of heme proteins: a femtosecond absorption study of hemoglobin, myoglobin, and protoheme. Biochemistry 27, 4049–1060 (1988).

    Article  CAS  PubMed  Google Scholar 

  24. Austin, R.H., Roberson, M.W. & Mansky, P. For-infrared perturbation of reaction rates in myoglobin at low temperatures. Phys. Rev. Lett. 62, 1912–195 (1989).

    Article  CAS  PubMed  Google Scholar 

  25. Sassaroli, M., Dasgupta, S. & Rousseau, D.L. Cryogenic stabilization of myoglobin photoproducts. J. biol. Chem. 261, 13704–13713 (1986).

    CAS  PubMed  Google Scholar 

  26. Gelin, B.R. & Karplus, M. Mechanism of tertiary structural changes in hemoglobin. Proc. natn. Acad. Sci. U.S.A. 74, 801–805 (1977).

    Article  CAS  Google Scholar 

  27. Perutz, M.F. Structure and mechanism of haemoglobin. A. Rev. Biochem. 48, 327–386 (1979).

    Article  CAS  Google Scholar 

  28. Petrich, J.W., Martin, J.-L., Houde, D., Poyart, C. & Orszag, A. Time-resolved raman spectroscopy with subpicosecond resolution: vibrational cooling and delocalization of strain energy in photodissociated (carbonmonoxy)hemoglobin. Biochemistry 26, 7914–7923 (1987).

    Article  CAS  PubMed  Google Scholar 

  29. Bangcharoenpaurpong, O., Schomaker, K.T. & Champion, P.M. A resonance raman investigation of myoglobin and hemoglobin.. J. Am. chem. Soc. 106, 5688–5698 (1984).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Franzen, S., Lambry, J., Bohn, B. et al. Direct evidence for the role of haem doming as the primary event in the cooperative transition of haemoglobin. Nat Struct Mol Biol 1, 230–233 (1994). https://doi.org/10.1038/nsb0494-230

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsb0494-230

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing