The solution structure of human epidermal growth factor

Abstract

The epidermal growth factors (EGFs)1–3are powerful mitogens for a wide variety of cells in culture4; human EGF (hEGF), known as urogastrone, also inhibits gastric acid secretion in vivo1. The transforming growth factors (TGF-α) are related to the EGF family both in sequence5 and activity6,7and EGF-like sequences are often observed in a wide range of functionally unrelated proteins8. Attempts to examine the structure of EGF by diffraction methods have not yet succeeded because of difficulties with crystallization. We report here a three-dimensional structure of a biologically active derivative (residues 1–48) of the 53-residue human EGF. An analysis of high resolution 1H nuclear magnetic resonance (NMR) spectra was used together with a combination of distance geometry, restrained energy minimization and restrained molecular dynamics methods. The three-dimensional structure provides a basis for understanding the properties of EGFs and for predicting the structures of homologous sequences in other proteins.

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References

  1. 1

    1. Gregory, H. Nature 257, 325–327 (1975). 2. Cohen, S. /. bioL Chem. 237, 1555–1562 (1962). 3. Simpson, R. J. et al Bur. J. Biochem. 153, 629–637 (1985). 4. Schlessinger, J. et al CRC Crit. Rev. Biochem. 14, 93–111 (1983). 5. Marquardt, H. et al Proc. natn. Acad. Scl U.S.A. 80, 4684–4688 (1983). 6. Marquardt, H. & Todaro, G. J. /. biol Chem. 257, 5220–5225 (1982). 7. Anzano, M. A. et al Cancer Res. 42, 4776–4778 (1982). 8. Doolittle, R. F. Trends biochem. Sci 10, 233–237 (1985). 9. Carver, J. A. et al FEBS Letts 205, 77–81 (1986). 10. Montelione, G. T., Wiithrich, K., Nice, E. C., Burgess, A. W. & Scheraga, H. A. Proc. natn. Acad. Sci. U.S.A. 83, 8594–8598 (1986). 11. Williamson, M. P., Havel, T. F. & Wiithrich, K. /. molec. Biol 182, 295–315 (1985). 12. Kaptein, R., Zuiderweg, E. R. P., Scheek, R. M., Boelens, R. & van Gunsteren, W. F. /. molec. Biol 182, 179–182 (1985). 13. Crippen, G. M. & Havel, T. Ada Crystallogr. sect. A 34, 282–284 (1978). 14. van Gunsteren, W. F. & Berendsen, H. J. C. Biochem. Soc. Trans. 10, 301–305 (1982). 15. Mayo, K. H., Schaudies, P., Savage, C. R., De Marco, A. & Kaptein, R. Biochem. J. 239, 13–18 (1986). 16. Hollenberg, M. D. & Gregory, H. Molec. PharmacoL 17, 314–320 (1980). 17. Komoriya, A. et al Proc. natn. Acad. Scl U.S.A. 81, 1351–1355 (1984). 18. Holladay, L. A., Savage, C. R., Cohen, S. & Puett, D. Biochemistry 15, 2624–2633 (1976). 19. Dayhoff, M. O. Atlas of Protein Sequence and Structure Vol. 5, suppl. 3, p. 85 (Natn. Biomed. Res. Found., Washington, 1978). 20. Giinzler, W. A. et al Hoppe–Seyler's Z. physioL Chem. 363, 1155–1165 (1982). 21. McMullen, B. A. et al Biochemistry 22, 2875–2884 (1983). 22. Esmon, N. L., DeBault, L. E. & Esmon, C. T. /. biol Chem. 258, 5548–5553 (1983). 23. Rees, D. J. G. D. Phil thesis, University of Oxford (1986). 24. Stenflo, J., Lundwall, A & Dahlback, B. Proc. natn. Acad. Sci U.S.A. 84, 368–372 (1987). 25. Kurachi, K. & Davie, E. W. Proc. natn. Acad. Sci U.S.A 79, 6461–6464 (1982). 26. McMuilen, B. A., Fujikawa, K. & Kisiel, W. Biochem. biophys. Res. Comm. 115,8–14 (1983). 27. Fernlund, P. & Stenflo, J. /. biol Chem. 257, 12170–12179 (1982). 28. Lundwall, A et al Proc. natn. Acad. Sci U.S.A. 83, 6716–6720 (1986). 29. Arlaud, G. J., Willis, A. C. & Gagnon, J. Biochem. J. 241, 711–720 (1987).

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Cooke, R., Wilkinson, A., Baron, M. et al. The solution structure of human epidermal growth factor. Nature 327, 339–341 (1987). https://doi.org/10.1038/327339a0

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