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Probing the Binding Sites in Crystals of Immunoglobulins

  • Allen B. Edmundson
  • Kathryn R. Ely
  • James N. Herron
  • Amy L. Gibson
Part of the Methodological Surveys in Biochemistry and Analysis book series (MSBA, volume 15B)

Abstract

In myeloma proteins from patient Mcg, 5 distinct 3-D structures assumed by one λ-type gene product have been defined by X-ray analysis: 2 conformational isomers in the Mcg Bence-Jones dimer crystallized in ammonium sulphate, 2 in the Mcg dimer crystallized in water (orthorhombic), and one in the Mcg IgG1 immunoglobulin (Ig). The 3 crystal systems differ in binding-cavity geometry, due to the conformational flexibility of the light and heavy chains. The Bence-Jones dimer binds 2 molecules of bis(DNP)lysine in solution and one in trigonal crystals. The IgG1 does not bind this ligand, nor does a λ-type Bence-Jones dimer from the patient Weir; but a hybrid dimer of the Weir and Mcg light chains binds one ligand molecule with the same affinity as the Mcg dimer. An explanation in 3-D terms is given.

Keywords

Light Chain Peptide Bond Ammonium Sulphate Binding Cavity Chemotactic Peptide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Edmundson, A.B., Ely, K.R., Girling, R.L., Abola, E.E., Schiffer, M., Westholm, F.A., Fausch, M.D. & Deutsch, H.F. (1974) Biochemistry 13, 3816–3827.CrossRefGoogle Scholar
  2. 2.
    Edmundson, A.B., Ely, K.R. & Herron, J.N. (1984) Mol. Immunol. 21, 561–576.CrossRefGoogle Scholar
  3. 3.
    Kranz, D.M., Herron, J.N. & Voss, E.W., Jr. (1982) J. Biol. Chem. 257, 6987–6995.Google Scholar
  4. 4.
    Gibson, A.L., Herron, J.N. & Edmundson, A.B. (1984) Fed. Proc. 43, 1546.Google Scholar
  5. 5.
    Navia, M.A., Segal, D.M., Padlan, E.A., Davies, D.R., Rao, N., Rudikoff, S. & Potter, M. (1979) Proc. Nat. Acad. Sci. 76, 4071–4074.CrossRefGoogle Scholar
  6. 6.
    Colman, P.M., Gough, K.H., Lilley, G.G., Blagrove, R.J., Webster, R.G., & Laver, W.G. (1981) J. Mol. Biol. 152, 609–614.CrossRefGoogle Scholar
  7. 7.
    Rose, D.R., Seaton, B.A., Petsko, G.A., Novotnÿ, J., Margolies, M.N., Locke, E. & Haber, E. (1983) J. Mol. Biol. 165, 203–206.CrossRefGoogle Scholar
  8. 8.
    Ballard, D.W., Lynn, S.P., Gardner, J.F. & Voss, E.W., Jr. (1984) J. Biol. Chem. 259, 3492–3498.Google Scholar
  9. 9.
    Fett, J.W., Deutsch, H.F. & Smithies, O. (1973) Immunochemistry 10, 115–118. CrossRefGoogle Scholar
  10. 10.
    Sarma, V.R., Silverton, E.W., Davies, D.R. & Terry, W.D. (1971) J. BioZ. Chem. 246, 3753–3759.Google Scholar
  11. 11.
    Silverton, E.W., Navia, M.A. & Davies, D.R. (1977) Proc. Nat. Acad. Sci. 74, 5140–5144.CrossRefGoogle Scholar
  12. 12.
    Marquart, M., Deisenhofer, J., Huber, R. & Palm, W. (1980) J. Mol. Biol. 141, 369–391.CrossRefGoogle Scholar
  13. 13.
    Ely, K.R., Colman, P.M., Abola, E.E., Hess, A.C., Peabody, D.S., Parr, D.M., Connell, G.E., Laschinger, C.A. & Edmundson, A.B. (1978) Biochemistry 17, 820–823.CrossRefGoogle Scholar
  14. 14.
    Edmundson, A.B., Wood, M.K., Schiffer, M., Hardman, K.D., Ainsworth, C.F., Ely, K.R. & Deutsch, H.F. (1970) J. Biol. Chem. 245, 2763–2764.Google Scholar
  15. 15.
    Rajan, S.S., Ely, K.R., Abola, E.E., Wood, M.K., Colman, P.M., Athay, R.J. & Edmundson, A.B. (1983) Mol. Immunol. 20, 787–799.CrossRefGoogle Scholar
  16. 16.
    Herzberg, 0. & Sussman, J.L. (1983) J. Appl. Cryst. 16, 144–150.CrossRefGoogle Scholar
  17. 17.
    Firca, J.R., Ely, K.R., Kremser, P., Westholm, F.A., Dorrington, K.J. & Edmundson, A.B. (1978) Biochemistry 17, 148–158.CrossRefGoogle Scholar
  18. 18.
    Peabody, D.5., Ely, K.R. & Edmundson, A.B. (1980) Biochemistry 19, 2827–2834.CrossRefGoogle Scholar
  19. 19.
    Kabat, E.A., Wu, T.T. & Bilofsky, H. (1977) J. Biol. Chem. 252, 6609–6616.Google Scholar
  20. 20.
    Ponstingl, H. & Hilschmann, N. (1971) Z. Physiol. Chem. 352, 859–877.CrossRefGoogle Scholar
  21. 21.
    Fett, J.W. & Deutsch, H.F. (1974) Biochemistry 13, 4102–4114.CrossRefGoogle Scholar
  22. 22.
    Putman, F.W., Whitley, E.J., Jr., Paul, C. & Davidson, J.N. (1973) Biochemistry 12, 3763–3780.CrossRefGoogle Scholar
  23. 23.
    Bertram, J., Gualtieri, R.J. & Osserman, E.F. (1980) in Amyloid and Amyloidosis (Glenner, G.G., Costa, P.P. & de Freitas, A.F., eds.), Excerpta Medica, Amsterdam, pp. 351–360.Google Scholar
  24. 24.
    Jabusch, J.R. & Deutsch, H.F. (1982) Mol. Immunol, 19, 901–906.CrossRefGoogle Scholar
  25. 24.
    Jabusch, J.R. & Deutsch, H.F. (1982) Mol. Immunol, 19, 901–906.CrossRefGoogle Scholar
  26. 24.
    Jabusch, J.R. & Deutsch, H.F. (1982) Mol. Immunol, 19, 901–906.CrossRefGoogle Scholar
  27. 27.
    Abola, E.E., Ely, K.R. & Edmundson, A.B. (1980) Biochemistry 19, 432–439.CrossRefGoogle Scholar
  28. 28.
    Ely, K.R., Herron, J.N. & Edmundson, A.B. (1983) Prog. Immunol. 5, 61–66.CrossRefGoogle Scholar
  29. 29.
    Schiffer, M., Girling, R.L., Ely, K.R. & Edmundson, A.B. (1973) Biochemistry 12, 4620–4631.CrossRefGoogle Scholar
  30. 30.
    Edmundson, A.B., Ely, K.R., Abola, E.E., Schiffer, M. & Panagiotopoulos, N. (1975) Biochemistry 14, 3953–3961.CrossRefGoogle Scholar
  31. 31.
    Poljak, R.J., Amzel, L.M., Chen, B.L., Phizackerley, R.P. & Saul, F. (1974) Proc. Nat. Acad. Sci. 71, 3440–3444.CrossRefGoogle Scholar
  32. 32.
    Connolly, M.L. (1983) Science 221, 709–713.CrossRefGoogle Scholar
  33. 33.
    Schiffmann, E., Showell, H.J., Corcoran, B.A., Ward, P.A., Smith, E. & Becker, E.L. (1975) J. Immunol. 114, 1831–1837.Google Scholar
  34. 34.
    Freer, R.J., Day, A.R., Muthukymaraswamy, N., Pinon, D., Wu, A., Showell, H.J. & Becker, E.L. (1982) Biochemistry 21, 257–263.CrossRefGoogle Scholar
  35. 35.
    Becker, E.L., Bleich, H.E., Day, A.R., Freer, R.J., Glasel, J.A., Latina, M. & Visintainer, J. (1979) Biochemistry 18, 4656–4668.CrossRefGoogle Scholar
  36. 36.
    Eggleston, D.S., Jeffs, P.W., Chodosh, D.F. & Heald, S.L. (1984) Abs., Am. Crystallogr. Assoc., Annual Mtg., Lexington, KY, PB4,36.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Allen B. Edmundson
    • 1
  • Kathryn R. Ely
    • 1
  • James N. Herron
    • 1
  • Amy L. Gibson
    • 1
  1. 1.Department of BiologyUniversity of UtahSalt Lake CityUSA

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