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Article
Nature 264, 415 - 420 (02 December 1976); doi:10.1038/264415a0

Crystallographic structure studies of an IgG molecule and an Fc fragment

Robert Huber, Johann Deisenhofer, Peter M. Colman*, Masaaki Matsushima & Walter Palm

Max-Planck-Institut für Biochemie, 8033 Martinsried, BRD and Physikalisch-Chemisches Institut der Technischen Universität München
Institut für Medizinische Biochemie der Universität Graz, Austria
*Present address: Institute of Inorganic Chemistry, University of Sydney 2060, Australia.

The crystal structures of a human IgG antibody molecule Kol and a human Fc fragment have been determined at 4-Å and 3.5-Å resolution respectively, by isomorphous replacement. The electron-density maps were interpreted in terms of immunoglobulin domains based on the Rei and McPC 603 models (Kol) and by model-building (Fc). The Fab parts of Kol have a different quaternary structure from that observed in isolated crystalline Fab fragments, there being no longitudinal V–C contact in Kol. The Fc part C terminal to the hinge is disordered in the Kol crystals. It is suggested that the Kol molecule is flexible in solution, whereas fragments are rigid. In the Fc fragment both CH3 and CH2 show the immunoglobulin fold. The CH3 dimer aggregates as CH1-CL while CH2 are widely separated from each other. The carbohydrate bound to Fc is in fixed position. From these structures a hypothetical liganded antibody molecule has been constructed, which is assumed to be rigid.

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References

1. Rutishauser, U., Cunningham, B. A., Bennet, C., Konigsberg, W. H., and Edelman, G. M., Biochemistry, 9, 3171–3181 (1970).
2. Fleischmann, J. B., Pain, R. H., and Porter, R. R., Archs Biochem. Biophys. Suppl., 1, 174 (1972).
3. Davies, D. R., Padlan, E. A., and Segal, D. M., A. Rev. Biochem., 44, 639–667 (1975).
4. Colman, P. M., Deisenhofer, J., Huber, R., and Palm, W., J. molec. Biol, 100, 257–282 (1976).
5. Deisenhofer, J., Colman, P. M., Huber, R., Haupt, H., and Schwick, G., Hoppe-Seyler's Z. Physiol. Chem., 357, 435–445 (1976).
6. Deisenhofer, J., Colman, P. M., Epp, O., and Huber, R., Hoppe-Seyler's Z. Physiol. Chem. 357, 1421–1434 (1976).
7. Epp, O. et al., Eur. J. Biochem., 45, 513–524 (1974).
8. Palm, W., and Hilschmann, N., Hoppe-Seyler's Z. Physiol. Chem., 356, 167–191
9. Palm, W., Hoppe-Seyler's Z. Physiol Chem., 355, 877–880 (1974); Palm, W., Hoppe-Seyler's Z. Physiol. Chem., 357, 795–789 (1976); Palm, W., Hoppe-Seyler's Z. Physiol. Chem. 357, 799–802 (1976).
10. Epp, O., Lattman, E. E., Schiffer, M., Huber, R., and Palm, W., Biochemistry, 14, 4943–4952 (1975).
11. Schiffer, M., Girling, R. L., Ely, K. R., and Edmundson, A. B., Biochemistry, 12, 4620–4631 (1973).
12. Strosberg, A. D., Fraser, K. J., Margolies, M. N., and Haber, E., Biochemistry, 11, 4978–4985 (1972).
13. Connell, G. E., and Porter, R. R., Biochem. J., 124, 53P (1971).
14. Kehoe, J. M., Bourgois, A., Capra, J. D., and Fougereau, M., Biochemistry, 13, 2499–2504 (1974).
15. Kornfeld, R., Keller, J., Baenziger, J., and Kornfeld, S., J. biol. Chem., 246, 3259–3268 (1971).
16. Marshall, R. D., A. Rev. Biochem., 41, 673–702 (1972).
17. Huber, R., Kukla, D., Rühlmann, A., Epp, O., and Formanek, H., Naturwissenschaften, 57, 389–392 (1970).
18. Kartha, G., Bello, J., and Harker, D., Nature, 213, 862–865 (1967).
19. Wyckoff, H. W. et al., J. biol. Chem., 242, 3749–3753 (1967).
20. Tschesche, H., Klauser, R., Cechová, D., and Yanáková, V., Hoppe-Seyler's Z. Physiol. Chem., 356, 7159–7164 (1974).
21. Jackson, R. L., and Hirs, C. H. W., J. biol. Chem., 245, 637–653 (1970).
22. Amzel, L. M., Poljak, R. J., Saul, F., Varga, J. M., and Richards, F. P., Proc. natn. Acad. Sci. U.S.A., 71, 1427–1430 (1974).
23. Segal, D. M., Padlan, E. A., Cohen, G. H., Rudikoff, S., Potter, M., and Davies, D. R., Proc. natn. Acad. Sci. U.S.A., 71, 4298–4302 (1974).
24. Edmundson, A. B., Ely, K. R., Abola, E. E., Schiffer, M., and Panagiotopoulos, N., Biochemistry, 14, 3953–3961 (1975).
25. Huber, R., Kukla, D., Bode, W., Schwager, P., Bartels, K., Deisenhofer, J., and Steigemann, W., J. molec. Biol., 89, 73–101 (1974).
26. Watanabe, S., Barnikol, H. U., Horn, J., Bertram, J., and Hilschmann, N., Hoppe-Seyler's Z. Physiol. Chem., 354 , 1505–1509 (1973).
27. Kratzin, H., Altevogt, P., Ruban, E., Kortt, A., Staroscik, K., and Hilschmann, N., Hoppe-Seyler's Z. Physiol. Chem., 356, 1337–1432 (1975).
28. Bennich, H., and Bahr-Lindström, H., Progress in Immunology II, 1 (edit. by Brent, L., and Holborow, J.), 49–58 (North-Holland, Amsterdam, Oxford, 1974).
29. Lopes, A. D., and Steiner, L. A., Fedn Proc., 32, 1003 (1973).
30. Fett, J. W., Deutsch, H. W., and Smithies, O., Immunochemistry, 10, 115–118 (1973).
31. Sarma, V. R., Silverton, E. W., Davies, D. R., and Terry, W. D., J. biol. Chem., 246, 3753–3759 (1971).
32. Valentine, R. C., and Green, N. M., J. molec. Biol., 27, 615–617 (1965).
33. Feinstein, A., and Rowe, A. J., Nature, 205, 147–149 (1965).
34. Yguerabide, J., Epstein, H. F., and Stryer, L., J. molec. Biol., 51, 573–590 (1970).
35. Noelken, E., Nelson, C. A., Buckley, C. E., and Tanford, C., J. biol. Chem., 240, 218–224 (1965).
36. Ashman, R. F., Kaplan, A. P., and Metzger, H., Immunochemistry, 8, 627–641 (1971).
37. Ashman, R. F., and Metzger, H., Immunochemistry, 8, 643–656 (1971).
38. Schlessinger, J., Steinberg, T. Z., Givol, D., Hochman, J., and Pecht, I., Proc. natn. Acad. Sci. U.S.A., 72, 2775–2779 (1975).
39. Jaton, J. C., Huser, H., Braun, D. G., Givol, W., Pecht, I., and Schlessinger, J., Biochemistry, 14, 5312–5315 (1975).
40. Pilz, I., Kratky, O., Licht, A., and Sela, M., Biochemistry, 12, 4998–5005 (1973).
41. Pilz, I., Kratky, O., Licht, A., and Sela, M., Biochemistry, 14, 1326–1333 (1975).
42. Tumerman, L. A., Nezlin, R. S., and Zagyanski, Y. A., FEBS Lett., 19, 290–292 (1972).
43. Warner, C., and Shumaker, V., Biochemistry, 9, 451–459 (1970).
44. Cathou, R. E., and Warner, T. C., Biochemistry, 9, 3149–3155 (1970).
45. Kelly, K. A., Schon, A. H., and Froese, A., Immunochemistry, 8, 613–625 (1971).
46. Levison, S. A., Hicks, A. N., Portmann, A. J., and Dandliker, W. B., Biochemistry, 14, 3778–3786 (1975).
47. Nisonoff, A., Wissler, F. C., and Woernley, D. L., Archs Biochem. Biophys., 88, 241–245 (1960).
48. Brown, J. C., and Koshland, M. E., Proc. natn. Acad. Sci. U.S.A., 72, 5111–5115 (1975).
49. Edmundson, A. B., Schiffer, M., Wood, M. K., Hardman, K. D., Ely, K. R., and Ainsworth, C. F., Cold Spring Harb. Symp. quant. Biol., 26, 427–432 (1972).



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