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Elbow motion in the immunoglobulins involves a molecular ball-and-socket joint


Studies by electron microscopy, fluorescence polarization, hydrodynamics and X-ray crystallography have demonstrated the ability of different parts of immunoglobulin molecules to move relative to each other. This movement facilitates the multiple interactions that antibodies make with polyvalent antigens and effector proteins. Comparisons of the atomic structures of immunoglobulins of the same sequence in different crystal environments, and of those with different sequences, have shown that the movements involve local changes in the conformation of the peptides linking different domains. These changes occur in (1) the hinge regions that link the Fab fragment to the Fc, and (2) the switch regions that link the VL–VH dimer to the CL–CH1 dimer1–15. We show here that in immunoglobulins of known structure, the movement of the VL–VH dimer relative to the CL–CH1 dimer also involves the interactions of three VH and two CH1 residues that form the molecular equivalent of a ball-and-socket joint. The almost absolute conservation in the sequences of immunoglobulins and T-cell receptors of the residues that form these interactions suggests that this is a general feature of functional importance.

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  1. Poljak, R. J., Amzel, L. M., Chen, B. L., Phizackerley, R. P. & Saul, F. Proc. natn. Acad. Sci. U.S.A. 71, 3440–3444 (1974).

    Article  ADS  CAS  Google Scholar 

  2. Colman, P. M., Deisenhofer, J., Huber, R. & Palm, W. J. molec. Biol. 100, 257–282 (1976).

    Article  CAS  Google Scholar 

  3. Silverton, E. W., Navia, M. A. & Davis, D. R. Proc. natn. Acad. Sci. U.S.A. 74, 5140–5149 (1977).

    Article  ADS  CAS  Google Scholar 

  4. Abola, E. E., Ely, K. R. & Edmundson, A. B. Biochemistry 19, 432–439 (1980).

    Article  CAS  Google Scholar 

  5. Saul, F. A., Amzel, L. M. & Poljak, R. J. J. biol. Chem. 253, 585–597 (1978).

    CAS  Google Scholar 

  6. Satow, Y., Cohen, G. H., Padlan, E. A. & Davies, D. R. J. molec. Biol. 190, 593–604 (1986).

    Article  CAS  Google Scholar 

  7. Marquart, M., Deisenhofer, J. & Huber, R. J. molec. Biol. 141, 369–391 (1980).

    Article  CAS  Google Scholar 

  8. Sun, S. E. et al. Proteins 1, 74–80 (1986).

    Article  Google Scholar 

  9. Sheriff, S. et al. Proc. natn. Acad. Sci. U.S.A. 84, 8075–8079 (1987).

    Article  ADS  CAS  Google Scholar 

  10. Amit, A. G., Mariuzza, R. A., Phillips, S. E. V. & Poljak, R. J. Science 233, 747–753 (1986).

    Article  ADS  CAS  Google Scholar 

  11. Colman, P. M. et al. Nature 326, 358–362 (1987).

    Article  ADS  CAS  Google Scholar 

  12. Cygler, M., Boodhoo, A., Lee, J. S. & Anderson, W. F. J. biol. Chem. 262, 643–648 (1987).

    CAS  PubMed  Google Scholar 

  13. Prased, L., Vandonselaar, M., Lee, J. S. & Delbaere, L. T. J. J. biol. Chem. 263, 2571–2574 (1987).

    Google Scholar 

  14. Vitali, J., Young, W. W., Schatz, V. B., Sobottka, S. E. & Kretsinger, R. H. J. molec. Biol. 198, 351–355 (1987).

    Article  CAS  Google Scholar 

  15. Davies, D. R. & Metzger, H. A. Rev. Immun. 1, 87–117 (1983).

    Article  CAS  Google Scholar 

  16. Bernstein, F. C. et al. J. molec. Biol. 112, 535–542 (1977).

    Article  CAS  Google Scholar 

  17. Rabat, E. A., Wu, T. T., Reid-Miller, M., Perry, H. M. & Gottesman, K. S. Sequences of Proteins of Immunological Interest 4th edn (Public Health Service, NIH, Washington DC, 1987).

    Google Scholar 

  18. Chien, Y. et al. Nature 312, 31–35 (1984).

    Article  ADS  CAS  Google Scholar 

  19. Hedrick, S. M., Nielsen, E. A., Kavaler, J., Cohen, D. I. & Davies, M. M. Nature 308, 153–158 (1984).

    Article  ADS  CAS  Google Scholar 

  20. Saito, H. et al. Nature 312, 36–40 (1984).

    Article  ADS  CAS  Google Scholar 

  21. Yanagi, Y. et al. Nature 308, 145–149 (1984).

    Article  ADS  CAS  Google Scholar 

  22. Saito, H. et al. Nature 309, 757–762 (1984).

    Article  ADS  CAS  Google Scholar 

  23. Chothia, C., Lesk, A. M., Dodson, G. G. & Hodgkin, D. C. Nature 302, 500–505 (1983).

    Article  ADS  CAS  Google Scholar 

  24. Lesk, A. M. & Chothia, C. J. molec. Biol. 174, 175–191 (1984).

    Article  CAS  Google Scholar 

  25. Elber, R. & Karplus, M. Science 235, 318–321 (1987).

    Article  ADS  CAS  Google Scholar 

  26. Perutz, M. F. Nature 228, 726–739 (1970).

    Article  ADS  CAS  Google Scholar 

  27. Baldwin, J. & Chothia, C. J. molec. Biol. 129, 175–200 (1979).

    Article  CAS  Google Scholar 

  28. Bennett, W. S. & Huber, R. Crit. Revs Biochem. 15, 291–384 (1984).

    Article  CAS  Google Scholar 

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Lesk, A., Chothia, C. Elbow motion in the immunoglobulins involves a molecular ball-and-socket joint. Nature 335, 188–190 (1988).

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