Russian Journal of Bioorganic Chemistry

, Volume 44, Issue 2, pp 193–198 | Cite as

Effect of Bioregulator Isatin on Protein–Protein Interactions Involving Isatin-Binding Proteins

  • P. V. Ershov
  • Y. V. Mezentsev
  • E. O. Yablokov
  • L. A. Kaluzhsky
  • A. V. Florinskaya
  • O. A. Buneeva
  • A. E. Medvedev
  • A. S. Ivanov
Article
  • 7 Downloads

Abstract

Isatin (2,3-dioxoindol) is an endogenous low-molecular-weight nonpeptide compound with a wide spectrum of biological and pharmacological activities. It is assumed that isatin acts through isatin-binding proteins. To date, more than a hundred of these proteins are known. Having a different structure and cellular and subcellular localization, they belong to different functional groups. Using the surface plasmon resonance technology, we found earlier that isatin affected the profile of intracellular amyloid-binding proteins and changed the stability of protein complexes in the model system. In fact, this indicates the selective effect of isatin on certain protein–protein interactions (PPI) that occur primarily with the participation of isatinbinding proteins. Therefore, we had formulated the hypothesis that isatin could be a regulator of a protein interactome. This study focuses on the verification of this assumption. Size-exclusion chromatography (SEC) profile of the rat liver tissue lysate along with mass-spectrometric protein identification has revealed 20 isatinbinding proteins that participate in the formation of the protein interactome. About 65 and 25% of them are involved in the formation of multimeric protein complexes and homo/heterodimers, respectively, and only 10% are detected as single molecules. The addition of isatin had a multidirectional effect on the profile of about half of the identified isatin-binding proteins. In some cases, the formation of protein complexes was induced, while in other cases the protein complexes were dissociated. This result confirms the hypothesis of the regulatory effect of isatin on certain PPIs. The data of this work in combination with our previous results allowed us to formulate an “interactomics image” of isatin as a bioregulator, which selectively controls both the formation and dissociation of a number of protein complexes. Two new isatin-dependent proteins were found in the work. This indicates that not all potential target proteins of the regulatory effect of isatin had been previously detected. The study of the molecular mechanisms of isatin action on PPI remains a difficult but priority task for future research.

Keywords

isatin isatin-binding proteins protein–protein interactions size-exclusion chromatography lysate profiling mass spectrometric identification 

Abbreviations

PPI

protein–protein interactions

SPR

surface plasmon resonance

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Robinson, J.A., Chembiochem., 2009, vol. 10, no. 6, pp. 971–973.CrossRefPubMedGoogle Scholar
  2. 2.
    Arkin, M.R., Tang, Y., and Wells, J.A., Chem. Biol., 2014, vol. 21, no. 9, pp. 1102–1114.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ivanov, A.S., Gnedenko, O.V., Molnar, A.A., Mezentsev, Y.V., Lisitsa, A.V., and Archakov, A.I., J. Bioinform. Comput. Biol., 2007, vol. 5, no. 2b, pp. 579–592.CrossRefPubMedGoogle Scholar
  4. 4.
    Ivanov, A.S., Veselovsky, A.V., Dubanov, A.V., and Skvortsov, V.S., Methods Mol. Biol., 2006, vol. 316, pp. 389–431.PubMedGoogle Scholar
  5. 5.
    Veselovsky, A.V., Ivanov, Y.D., Ivanov, A.S., Archakov, A.I., Lewi, P., and Janssen, P., J. Mol. Recognit., 2002, vol. 15, no. 6, pp. 405–422.CrossRefPubMedGoogle Scholar
  6. 6.
    Veselovsky, A.V. and Ivanov, A.S., Curr. Drug Targets Infect. Disord., 2003, vol. 3, pp. 33–40.CrossRefPubMedGoogle Scholar
  7. 7.
    Ershov, P.V., Gnedenko, O.V., Mol’nar, A.A., Lisitsa, A.V., Ivanov, A.S., and Archakov, A.I., Biomed. Khim., 2009, vol. 55, no. 4, pp. 462–478.PubMedGoogle Scholar
  8. 8.
    Ershov, P.V., Gnedenko, O.V., Mol’nar, A.A., Lisitsa, A.V., Ivanov, A.S., and Archakov, A.I., Biomed. Khim., 2012, vol. 58, no. 1, pp. 43–49.CrossRefPubMedGoogle Scholar
  9. 9.
    Buneeva, O.A., Gnedenko, O.V., Medvedeva, M.V., Ivanov, A.S., and Medvedev, A.E., Biomed. Khim. 2016, vol. 62, no. 6, pp. 720–724.CrossRefPubMedGoogle Scholar
  10. 10.
    Buneeva, O.A., Gnedenko, O.V., Medvedeva, M.V., Ivanov, A.S., and Medvedev, A.E., Biomed. Khim., 2016, vol. 62, no. 2, pp. 160–163.CrossRefPubMedGoogle Scholar
  11. 11.
    Ershov, P.V., Yablokov, E.O., Mezentsev, Yu.V., Kaluzhskii, L.A., Florinskaya, A.V., Veselovskii, A.V., Gnedenko, O.V., Gilep, A.A., Usanov, S.A., Medvedev, A.E., and Ivanov, A.S., Biomed. Khim., 2017, vol. 63, no. 2, pp. 170–175.CrossRefPubMedGoogle Scholar
  12. 12.
    Medvedev, A.E., Clow, A., Sandler, M., and Glover, V., Biochem. Pharmacol., 1996, vol. 52, pp. 385–391.CrossRefPubMedGoogle Scholar
  13. 13.
    Medvedev, A., Igosheva, N., Crumeyrolle-Arias, M., and Glover, V., Stress, 2005, vol. 8, no. 3, pp. 175–183.CrossRefPubMedGoogle Scholar
  14. 14.
    Medvedev, A., Buneeva, O., and Glover, V., Biol. Targets Ther., 2007, vol. 1, no. 2, pp. 151–162.Google Scholar
  15. 15.
    Crumeyrolle-Arias, M., Buneeva, O., Zgoda, V., Kopylov, A., Cardona, A., Tournaire, M.-C., Pozdnev, V., Glover, V., and Medvedev, A., J. Neurosci. Res., 2009, vol. 87, pp. 2763–2772.CrossRefPubMedGoogle Scholar
  16. 16.
    Buneeva, O., Gnedenko, O., Zgoda, V., Kopylov, A., Glover, V., Ivanov, A., Medvedev, A., and Archakov, A., Proteomics, 2010, vol. 10, pp. 23–37.CrossRefPubMedGoogle Scholar
  17. 17.
    Buneeva, O.A., Kopylov, A.T., Tikhonova, O.V., Zgoda, V.G., Medvedev, A.E., and Archakov, A.I., Biochemistry (Moscow), 2012., vol. 77, no. 11, pp. 1326–1338.CrossRefGoogle Scholar
  18. 18.
    Medvedev, A.E., Buneeva, O.A., Kopylov, A.T., Mitkevich, V.A., Kozin, S.A., Zgoda, V.G., and Makarov, A.A., Biochimie, 2016, vols. 128–129, no. 1, pp. 55–58.CrossRefPubMedGoogle Scholar
  19. 19.
    Wan, C., Borgeson, B., Phanse, S., Tu, F., Drew, K., Clark, G., Xiong, X., Kagan, O., Kwan, J., Bezginov, A., Chessman, K., Pal, S., Cromar, G., Papoulas, O., Ni, Z., Boutz, D.R., Stoilova, S., Havugimana, P.C., Guo, X., Malty, R.H., Sarov, M., Greenblatt, J., Babu, M., Derry, W.B., Tillier, E.R., Wallingford, J.B., Parkinson, J., Marcotte, E.M., and Emili, A., Nature, 2015, vol. 525, no. 7569, pp. 339–344.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Havugimana, P.C., Hart, G.T., Nepusz, T., Yang, H., Turinsky, A.L., Li, Z., Wang, P.I., Boutz, D.R., Fong, V., Phanse, S., et al., Cell, 2012, vol. 150, no. 5, pp. 1068–1081.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sun, T., Hayakawa, K., Bateman, K.S., and Fraser, M.E., J. Biol. Chem., 2010, vol. 285, no. 35, pp. 27418–27428.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Sun, T., Hayakawa, K., and Fraser, M.E., Acta Crystallogr. Sect. F: Struct. Biol. Cryst. Communs., 2011, vol. 67, pp. 1168–1172.CrossRefGoogle Scholar
  23. 23.
    Singh, M., Richards, E.G., Mukherjee, A., and Srere, P.A., J. Biol. Chem., 1976, vol. 251, no. 17, pp. 5242–5250.PubMedGoogle Scholar
  24. 24.
    Schliebs, W., Thanki, N., Eritja, R., and Wierenga, R., Protein Sci., 1996, vol. 5, no. 2, pp. 229–239.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Borchert, T.V., Abagyan, R., Jaenicke, R., and Wierenga, R.K., Proc. Natl. Acad. Sci. U. S. A., 1994, vol. 91, no. 4, pp. 1515–1518.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Karlberg, T., Collins, R., Berg, S., Flores, A., Hammarstrom, M., Hogbom, M., Holmberg Schiavone, L., and Uppenberg, J., Acta Crystallogr. D. Biol. Crystallogr., 2008, vol. 64, pp. 279–286.CrossRefPubMedGoogle Scholar
  27. 27.
    Liu, R., Su, R., Liang, M., Huang, R., Wang, M., Qi, W., and He, Z., Curr. Med. Chem., 2012, vol. 19, no. 24, pp. 4157–4174.CrossRefPubMedGoogle Scholar
  28. 28.
    Arsequell, G. and Planas, A., Curr. Med. Chem., 2012, vol. 19, no. 15, pp. 2343–2355.CrossRefPubMedGoogle Scholar
  29. 29.
    Ono, H., Yoshimura, N., Sato, M., and Tuboi, S., J. Biol. Chem., 1985, vol. 260, no. 6, pp. 3402–3407.PubMedGoogle Scholar
  30. 30.
    Torres-Bugeau, C.M., Ávila, C.L., Raisman-Vozari, R., Papy-Garcia, D., Itri, R., Barbosa, L.R., Cortez, L.M., Sim, V.L., and Chehin, R.N., J. Biol. Chem., 2012, vol. 287, no. 4, pp. 2398–2409.CrossRefPubMedGoogle Scholar
  31. 31.
    Medvedev, A.E., Buneeva, O.A., Kopylov, A.T., Gnedenko, O.V., Medvedeva, M.V., Kozin, S.A., Ivanov, A.S., Zgoda, V.G., and Makarov, A.A., Int. J. Mol. Sci., 2015, vol. 16, no. 1, pp. 476–495.CrossRefGoogle Scholar
  32. 32.
    Wisniewski, J.R., Zougman, A., Nagaraj, N., and Mann, M., Nature Methods, 2009, vol. 6, pp. 359–362.CrossRefPubMedGoogle Scholar
  33. 33.
    Ivanov, A.S., Ershov, P.V., Molnar, A.A., Mezentsev, Yu.V., Kaluzhskiy, L.A., et al., Russ. J. Bioorg. Chem., 2016, vol. 42, pp. 14–21.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • P. V. Ershov
    • 1
  • Y. V. Mezentsev
    • 1
  • E. O. Yablokov
    • 1
  • L. A. Kaluzhsky
    • 1
  • A. V. Florinskaya
    • 1
  • O. A. Buneeva
    • 1
  • A. E. Medvedev
    • 1
  • A. S. Ivanov
    • 1
  1. 1.Orekhovich Institute of Biomedical ChemistryMoscowRussia

Personalised recommendations