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Role of cis- and trans-interactions in manifestations of amyloidogenic properties of variable domains of Bence-Jones proteins TIM and LUS

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Abstract

Intact Bence-Jones proteins TIM and LUS under simulated physiological conditions (10 mM phosphate buffer, pH 7.0, 100 mM NaCl, 37°C) did not display amyloidogenic properties. However, their isolated variable domains exhibit these qualities in full measure. Therefore, both intact proteins and their variable domains were studied using a complex of physical methods (scanning microcalorimetry, analytical centrifugation, optics) that allowed us to assess the stability of their tertiary and quaternary structures. The experimentally obtained thermodynamic functions indicated that the stability of iso-lated variable domains of TIM and LUS was comparable to the stability of similar domains in amyloidogenic proteins described earlier. However, inside the whole protein their stability was comparable to the stability of VL domains of ordinary Bence-Jones proteins. The decreased stability of the isolated variable domains of TIM and LUS was shown to be due both to weak interactions between a pair of variable domains (trans -interaction) and to a natural lack of interaction with the con-stant domains (cis-interaction).

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Abbreviations

CL :

light chain constant domains

DSS:

bis(N-hydroxysuccinimide suberate) ester

DSS-FV :

a fragment with variable domains of the light chain cross-linked with the corresponding reagent

Fb-subunit (fragment):

a structure formed by a pair of constant domains CL-CL

FITC:

fluorescein isothio-cyanate

Fv-subunit (fragment):

a structure formed by a pair of variable domains VL-VL

FITC-V(C)L :

FITC-labeled variable (constant) domain

IgG:

immunoglobulins of G class

VL :

light chain variable domains

References

  1. Falk, R. H., Comenzo, R. L., and Skinner, M. (1997) N. Engl. J. Med., 337, 898–909.

    Article  PubMed  CAS  Google Scholar 

  2. Huff, M. E., Balch, W. E., and Kelly, J. W. (2003) Curr. Opin. Struct. Biol., 13, 674–682.

    Article  PubMed  CAS  Google Scholar 

  3. Pozzi, C., and Locatelli, F. (2002) Semin. Nephrol., 22, 319–330.

    PubMed  CAS  Google Scholar 

  4. Helms, L. R., and Wetzel, R. (1995) Protein Sci., 4, 2073–2081.

    Article  PubMed  CAS  Google Scholar 

  5. Wall, J., Schell, M., Murphy, C., Hrncic, R., Stevens, F. J., and Solomon, A. (1999) Biochemistry, 38, 14101–14108.

    Article  PubMed  CAS  Google Scholar 

  6. Raffen, R., Dieckman, L. J., Szpunar, M., Wanschl, C., Rokkuluri, P. R., Dave, R., Wilkins, Stevens, P., Cai, X., Schiffer, M., and Stevens, F. J. (1999) Protein Sci., 8, 509–517.

    Article  PubMed  CAS  Google Scholar 

  7. Kim, Y., Wall, J. S., Meyer, J., Murphy, C., Randolph, T. W., Manning, M., Solomon, A., and Carpenter, J. F. (2000) J. Biol. Chem., 275, 1570–1574.

    Article  PubMed  CAS  Google Scholar 

  8. Solomon, A., Weiss, D. T., Murphy, C. L., Hrncic, R., Wall, J. S., and Schell, M. (1998) Proc. Natl. Acad. Sci. USA, 95, 9547–9551.

    Article  PubMed  CAS  Google Scholar 

  9. Tishchenko, V. M., Khristoforov, V. S., and Bliznyukov, O. P. (2009) Mol. Biol., 43, 148–156.

    Article  CAS  Google Scholar 

  10. Tishchenko, V. M. (2011) Mol. Biol., 45, 1055–1064.

    Article  CAS  Google Scholar 

  11. Epp, O., Lattman, E. E., Schiffer, M., Huber, R., and Palm, W. (1975) Biochemistry, 14, 943–952.

    Article  Google Scholar 

  12. Chang, C. H., Short, M. T., Westholm, F. A., Stevens, F. J., Wang, B. C., Furey, W., Jr., Solomon, A., and Schiffer, M. (1985) Biochemistry, 24, 4890–4897.

    Article  PubMed  CAS  Google Scholar 

  13. Schiffer, M., Chang, C.-H., Naik, V. M., and Stevens, F. J. (1988) J. Mol. Biol., 203, 799–802.

    Article  PubMed  CAS  Google Scholar 

  14. Miller, S. (1990) J. Mol. Biol., 216, 965–973.

    Article  PubMed  CAS  Google Scholar 

  15. Bliznyukov, O. P., Kozmin, L. D., Vysotskaya, L. L., Golenkov, A. K., Tishchenko, V. M., Samoilovich, M. P., and Klimovich, V. P. (2005) Biochemistry (Moscow), 70, 458–466.

    Article  CAS  Google Scholar 

  16. Laemmli, U. K. (1970) Nature, 227, 680–685.

    Article  PubMed  CAS  Google Scholar 

  17. Laurell, C. B. (1965) Analyt. Biochem., 10, 358–361.

    Article  PubMed  CAS  Google Scholar 

  18. Zav’yalov, V. P., Troitsky, G. V., Khechinashvili, N. N., and Privalov, P. L. (1977) Biochim. Biophys. Acta, 492, 102–111.

    Article  PubMed  Google Scholar 

  19. Tishchenko, V. M. (2001) Biochemistry (Moscow), 66, 1352–1355.

    Article  Google Scholar 

  20. Tischenko, V. M., Abramov, V. M., and Zav’yalov, V. P. (1998) Biochemistry, 37, 5576–5581.

    Article  PubMed  CAS  Google Scholar 

  21. Tischenko, V. M., and Zav’yalov, V. P. (2002) Immunol. Lett., 84, 241–245.

    Article  PubMed  CAS  Google Scholar 

  22. Eulitz, M., Chang, L.-Y., Zirkel, C., Schell, M., Weiss, D. T., and Solomon, A. (1995) J. Immunol., 154, 3256–3265.

    PubMed  CAS  Google Scholar 

  23. Wall, J., Murphy, C. L., and Solomon, A. (1999) Methods Enzymol., 309, 204–216.

    Article  PubMed  CAS  Google Scholar 

  24. Yphantis, D. A. (1964) Biochemistry, 3, 297–317.

    Article  PubMed  CAS  Google Scholar 

  25. Van Holde, K. E., and Baldwin, R. L. (1958) J. Phys. Chem., 62, 734–743.

    Article  Google Scholar 

  26. Bowen, T. (1971) in An Introduction to Ultracentrifugation (Degly, S., ed.) Wiley-Interscience, London-N.-Y.-Sydney-Toronto, pp. 107–108.

  27. Tishchenko, V. M. (2000) Mol. Biol., 34, 116–122.

    CAS  Google Scholar 

  28. Privalov, P. L., and Potekhin, S. A. (1986) Methods Enzymol., 131, 4–51.

    Article  PubMed  CAS  Google Scholar 

  29. Wetzel, R. (1997) Adv. Prot. Chem., 50, 183–242.

    Article  CAS  Google Scholar 

  30. Tishchenko, V. M. (2012) Biofizika, in press.

    Google Scholar 

  31. Filimonov, V. V., and Rogov, V. V. (1996) J. Mol. Biol., 255, 767–777.

    Article  PubMed  CAS  Google Scholar 

  32. Potekhin, S. A., and Kovrigin, E. L. (1998) Biofizika, 43, 223–232.

    PubMed  CAS  Google Scholar 

  33. Potekhin, S. A., Loseva, O. I., Tiktopulo, E. I., and Dobritsa, A. P. (1999) Biochemistry, 38, 4121–4127.

    Article  PubMed  CAS  Google Scholar 

  34. Tischenko, V. M., Zav’yalov, V. P., Medgyesi, G. A., Potekhin, S. A., and Privalov, P. L. (1982) Eur. J. Biochem., 126, 517–521.

    Article  PubMed  CAS  Google Scholar 

  35. Zav’yalov, V. P., and Tishchenko, V. M. (1991) Scand. J. Immunol., 33, 755–762.

    Article  PubMed  Google Scholar 

  36. Tischenko, V. M., and Zav’yalov, V. P. (2003) Immunol. Lett., 86, 281–285.

    Article  PubMed  CAS  Google Scholar 

  37. Privalov, P. L. (1979) Adv. Prot. Chem., 33, 167–241.

    Article  CAS  Google Scholar 

  38. Privalov, P. L. (1982) Adv. Prot. Chem., 35, 1–104.

    Article  CAS  Google Scholar 

  39. Privalov, P. L., and Makhatadze, G. I. (1992) J. Mol. Biol., 224, 715–723.

    Article  PubMed  CAS  Google Scholar 

  40. Tischenko, V. M. (1999) in Abst. XIth Int. Conf. on Small-Angle Scattering, Brookhaven National Laboratory, N. Y., p. 93.

    Google Scholar 

  41. Tishchenko, V. M. (2013) Mol. Biol., in press.

    Google Scholar 

  42. Del Pozo Yauner, L., Ortiz, E., Sanchez, R., Sanchez-Lopez, R., Guereca, L., Murphy, C. L., Allen, A., Wall, J. S., Fernandez-Velasco, D. A., Solomon, A., and Becerril, B. (2008) Proteins, 72, 684–692.

    Article  PubMed  Google Scholar 

  43. Rowe, E. S., and Tanford, C. (1970) Biochemistry, 24, 4822–4827.

    Google Scholar 

  44. Goto, Y., Ichimura, N., and Hamaguchi, K. (1988) Biochemistry, 27, 1670–1677.

    Article  PubMed  CAS  Google Scholar 

  45. Pace, C. N., Shirley, B. A., and Thomson, J. A. (1989) in Protein Structure: A Practical Approach (Creighton, T. E., ed.) IRL Press, Oxford, pp. 311–330.

  46. Blancas-Mejia, L. M., Tellez, L. A., del Pozo-Yauner, L., Becerril, B., Sanchez-Ruiz, J. M., and Fernandez-Velasco, D. A. (2009) J. Mol. Biol., 386, 1153–1166.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    V. M. Tishchenko

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Correspondence to V. M. Tishchenko.

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Original Russian Text © V. M. Tishchenko, 2013, published in Biokhimiya, 2013, Vol. 78, No. 4, pp. 481–491.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM12-272, January 27, 2013.

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Tishchenko, V.M. Role of cis- and trans-interactions in manifestations of amyloidogenic properties of variable domains of Bence-Jones proteins TIM and LUS. Biochemistry Moscow 78, 368–376 (2013). https://doi.org/10.1134/S0006297913040056

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  • DOI: https://doi.org/10.1134/S0006297913040056

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