Laboratory of Structural Biochemistry of Proteins

levitsky_1 Dmitriy I. Levitsky
Professor, Dr.Sci. (Biology)
Head of Laboratory
INBI, build. 1, room 334
Телефон +7 (495) 952-13-84
E-Mail levitsky@inbi.ras.ru

Main directions of studies and achievements:

The laboratory consists of many scientific group, and each group has its own direction of studies:

1) Group of Prof. D.I. Levitsky
Structural and functional studies on the main muscle proteins – myosin, actin, and tropomyosin, including detailed analysis of the thermal unfolding of these proteins using differential scanning calorimetry (DSC) in combination with other methods and approaches.

2) Group of Prof. B.I. Kurganov
The study of the mechanisms of protein aggregation and mechanisms of protective action of chaperones of the proteinous nature (small heat shock proteins) and low-molecular-weight chemical chaperones.
A new mechanism of the process of amorphous protein aggregation has been proposed. The initial stage of the aggregation process is the formation of the start aggregates involving hundreds of denatured protein molecules; further aggregation proceeds as a result of sticking of the start aggregates and aggregates of higher order in diffusion-limited regime. The methods of the quantitative estimation of the anti-aggregation activity for molecular chaperones and chemical chaperones have been elaborated.

3) Group of Dr. N.A. Chebotareva, Dr. Biol. Sci.
The study of anti-aggregation activity of small heat shock proteins under crowded conditions.
We showed that crowding stimulates association of sHsp—client protein complexes into large-sized aggregates thus diminishing the apparent anti-aggregation activity of sHsps. Nevertheless, it was also shown that relatively small complexes between dissociated forms of sHsps and client proteins are responsible for anti-aggregation function under crowded conditions.

4) Group of Prof. A.A. Zamyatnin
The study (in silico) of the structure-functional properties of endogenous oligopeptides and dynamics of exogenous protein fragment formation using computer programs for the comparison of amino acid residue sequences of different databases in according to a predetermined criterion and of protein fragmantation in silico. Maintenance (improving and updating) of  the EROP-Moscow endogenous oligopeptide database with Internet access – http://erop.inbi.ras.ru

 

Selected publications:

1.  Nevzorov I.A., Nikolaeva O.P., Kainov Y.A., Redwood C.S., Levitsky D.I. Conserved non-canonical residue Gly-126 confers instability to the middle part of the tropomyosin molecule. – Journal of Biological Chemistry, 2011, v. 286, № 18, p. 15766–15772.

2.  Nevzorov I.A., Levitsky D.I. Tropomyosin: Double helix from the protein world. – Biochemistry (Moscow), 2011, v. 76, № 13, p. 1507–1527.

3.  Eronina T., Borzova V., Maloletkina O., Kleymenov S., Asryants R., Markossian K., Kurganov B. A protein aggregation based test for screening of the agents affecting thermostability of proteins. – PLoS One, 2011, v. 6(7): e22154. doi: 10.1371/journal.pone.0022154.

4.  Roman S.G., Chebotareva N.A., Eronina T.B., Kleymenov S.Yu., Makeeva V.F., Muranov K.O., Poliansky N.B., Kurganov B.I. Does crowded cell-like environment reduce the chaperone-like activity of alpha-crystallin? – Biochemistry, 2011, v. 50, № 49, p. 10607-10623.

5.  Artemova N.V., Bumagina, Z.M., Stein-Margolina V.A, Gurvits B.Ya. Acceleration of protein aggregation by amphiphilic peptides: Transformation of supramolecular structure of the aggregates. – Biotechnology Progress, 2011, v. 27, № 2, p. 359–368.

6.  Muranov K.O., Maloletkina O.I., Poliansky N.B., Markossian K.A., Kleymenov S.Yu., Rozhkov S.P., Goryunov A.S., Ostrovsky M.A., Kurganov B.I. Mechanism of aggregation of UV-irradiated betaL-crystallin. – Experimental Eye Research, 2011, v. 92, No. 1, p. 76-86.

7.  Sluchanko N.N., Gusev N.B. Probable participation of 14-3-3 in tau protein oligomerization and aggregation. – J. Alzheimers Dis., 2011, v. 27, p. 467–476.

8.  Sluchanko N.N., Sudnitsyna M.V., Seit-Nebi A.S., Antson A.A., Gusev N.B. Properties of the monomeric form of human 14-3-3zeta protein and its interaction with tau and HspB6. – Biochemistry, 2011, v. 50, p. 9797-9808.

9.  Sluchanko N.N., Artemova N.V., Sudnitsyna M.V., Safenkova I.V., Antson A.A., Levitsky D.I., Gusev N.B. Monomeric 14-3-3ζ has a chaperone-like activity and is stabilized by phosphorylated HspB6. – Biochemistry, 2012, v. 51, p. 6127-6138.

10. Sluchanko N.N., Gusev N.B. Oligomeric structure of 14-3-3 protein: what do we know about monomers? FEBS Letters, 2012, v. 586, p. 4249-4256.

11. Artemova N., Stein-Margolina V., Smirnova E., Gurvits B. Formation of supramolecular structures of a native-like protein in the presence of amphiphilic peptides: variations in aggregate morphology. – FEBS Letters, 2012, v. 586, № 2, p. 186-190.

12. Roman, S.G., Chebotareva, N.A., Kurganov, B.I. Concentration dependence of chaperone-like activities of alpha-crystallin, alphaB-crystallin and proline. – International Journal of Biological Macromolecules, 2012, v. 50, No. 5, p. 1341-1345.

13. Maloletkina, O.I., Markossian, K.A., Chebotareva, N.A., Asryants, R.A., Kleymenov, S.Yu., Poliansky, N.B., Muranov, K.O., Makeeva, V.F., Kurganov, B.I. Kinetics of aggregation of UV-irradiated glyceraldehyde-3-phosphate dehydrogenase from rabbit skeletal muscle: Effect of agents possessing chaperone-like activity. – Biophysical Chemistry, 2012, v. 163-164, p. 11-20.

14. Zamyatnin A.A., Voronina O.L. Food protein fragments are regulatory oligopeptides – Biochemistry (Moscow), 2012, v. 77, № 5, p. 502–510.

15. Pivovarova A.V, Chebotareva N.A., Kremneva E.V., Lappalainen P., Levitsky D.I. Effects of actin-binding proteins on the thermal stability of monomeric actin. – Biochemistry, 2013, v. 52, № 1, p. 152–160.

16. Sluchanko N.N., Chebotareva N.A., Gusev N.B. Modulation of 14-3-3/phosphotarget interaction by physiological concentrations of phosphate and glycerophosphates. – PLoS One, 2013, v. 8(8): e72597. doi:10.1371/journal.pone.0072597

17. Borzova V.A., Markossian K.A., Kara D.A., Chebotareva N.A., Makeeva V.F., Poliansky N.B., Muranov K.O., Kurganov B.I. Quantification of anti-aggregation activity: a test-system based on dithiothreitol-induced aggregation of bovine serum albumin. – PloS One, 2013, v. 8(9): e74367. doi: 10.1371/journal.pone.0074367.

18. Smirnova E., Safenkova I., Stein-Margolina V., Shubin V., Gurvits B. L. Arginine induces protein aggregation and transformation of supramolecular structures of the aggregates. – Amino Acids, 2013, v. 45, p. 845–855.

19. Smirnova E., Chebotareva N., Gurvits B. Transient transformation of oligomeric structure of alpha-crystallin during its chaperone action. – International Journal of Biological Macromolecules, 2013, v. 55, p. 62–68.

20. Bekasova O.D., Safenkova I.V., Misurkin P.I., Timofeeva V.A., Kurganov B.I. Effect of cadmium sulfide quantum dots on physical properties of R-phycoerythrin as a protein matrix. – Protein and Peptide Letters, 2013, v. 20, No. 1, p. 2-7.

21. Chebotareva N.A., Eronina T.B., Roman S.G., Poliansky N.B., Muranov K.O., Kurganov B.I. Effect of crowding and chaperones on self-association, aggregation and reconstitution of apophosphorylase b. – International Journal of Biological Macromolecules, 2013, v. 60, p. 69-76.

22. Bekasova O.D., Shubin V.V., Safenkova I.V., Kovalyov L.I., Kurganov B.I. Structural changes in R-phycoerythrin upon CdS quantum dot synthesis in tunnel cavities of protein molecules. – International Journal of Biological Macromolecules. 2013, vol. 62, p. 623-628.

23. Kurganov B.I. Antiaggregation activity of chaperones and its quantification. – Biochemistry (Moscow), 2013, v. 78, No. 13, p. 1554-1566.

24. Matyushenko A.M., Artemova N.V., Shchepkin D.V., Kopylova G.V., Bershitsky S.Y., Tsaturyan A.K., Sluchanko N.N., Levitsky D.I. Structural and functional effects of two stabilizing substitutions, D137L and G126R, in the middle part of α-tropomyosin molecule. – FEBS Journal, 2014, v. 281, p. 2004-2016.

25. Smirnova E., Safenkova I., Stein-Margolina V., Shubin V., Gurvits B. Can aggregation of insulin govern its fate in the intestine? Implications for oral delivery of the drug. – International Journal of Pharmaceutics. 2014, v. 471, № 1-2, p. 65-68.

26. Sluchanko N.N., Roman S.G., Chebotareva N.A., Gusev N.B. Chaperone-like activity of monomeric human 14-3-3zeta on different protein substrates. – Archives of Biochemistry and Biophysics, 2014, v. 549, p. 32-39.

27. Eronina T.B., Chebotareva N.A., Roman S.G., Kleymenov S.Yu., Makeeva V.F., Poliansky N.B., Muranov K.O., Kurganov B.I. Thermal denaturation and aggregation of apoform of glycogen phosphorylase b. Effect of crowding agents and chaperones. – Biopolymers, 2014, v. 101, No. 5, p. 504-516.

28. Borzova V.A., Markossian K.A., Kurganov B.I. Relationship between the initial rate of protein aggregation and the lag period for amorphous aggregation. – International Journal of Biological Macromolecules, 2014, v. 68, p. 144-150.

29. Eronina T.B., Chebotareva N.A., Sluchanko N.N., Mikhaylova V.V., Makeeva V.F., Roman S.G., Kleymenov S.Y., Kurganov B.I. Dual effect of arginine on aggregation of phosphorylase kinase. – International Journal of Biological Macromolecules, 2014, vol. 68, p. 225-323.

30. Logvinova D.S., Markov D.I., Nikolaeva O.P., Sluchanko N.N., Ushakov D.S., Levitsky D.I. Does interaction between the motor and regulatory domains of the myosin head occur during ATPase cycle? Evidence from thermal unfolding studies on myosin subfragment 1. – PLoS One, 2015, v. 10(9): e0137517. doi:10.1371/journal.pone.0137517.

31. Matyushenko A.M., Artemova N.V., Sluchanko N.N., Levitsky D.I. Effects of two stabilizing substitutions, D137L and G126R, in the middle part of α-tropomyosin on the domain structure of its molecule. – Biophysical Chemistry, 2015, v. 196, № 1, p. 77–85.  doi: 10.1016/j.bpc.2014.10.001

32. Sluchanko N.N., Chebotareva N.A., Gusev N.B. Quaternary structure of human small heat shock protein HSPB6 (Hsp20) in crowded media modeled by trimethylamine N-oxide (TMAO): Effect of protein phosphorylation. – Biochimie, 2015, v. 108, p. 68-75.

33. Smirnova E., Safenkova I., Stein-Margolina V., Shubin V., Polshakov V., Gurvits B. pH-responsive modulation of insulin aggregation and structural transformation of the aggregates. – Biochimie, 2015, v. 109, p. 49-59.

34. Borzova V.A., Markossian K.A., Muranov K.O., Polyansky N.B., Kleymenov S.Yu., Kurganov B.I. Quantification of anti-aggregation activity of UV-irradiated alpha-crystallin. – International Journal of Biological Macromolecules, 2015, v. 73, p. 84-91.

35. Chebotareva N.A., Eronina T.B., Sluchanko N.N., Kurganov B.I. Effect of Ca(2+) and Mg(2+) ions on oligomeric state and chaperone-like activity of alphaB-crystallin in crowded media. – International Journal of Biological Macromolecules, 2015, v. 76, p. 86-93.

36. Borzova V.A., Markossian K.A., Kara D.A., Kurganov B.I. Kinetic regime of dithiothreitol-induced aggregation of bovine serum albumin. – International Journal of Biological Macromolecules, 2015, v. 80, p. 130-138.

37. Chebotareva N.A., Filippov D.O., Kurganov B.I. Effect of crowding on several stages of protein aggregation in test systems in the presence of alpha-crystallin. – International Journal of Biological Macromolecules, 2015, v. 80, p. 358-365.

38. Sudnitsyna M.V., Sluchanko N.N., Gusev N. B. HspB6 (Hsp20) as a versatile molecular regulator. – The Big Book on Small Heat Shock Proteins (Springer), 2015, Chapter 9, p. 229-253.

39. Sluchanko N.N., Uversky V.N. Hidden disorder propensity of the N-terminal segment of universal adapter protein 14-3-3 is manifested in its monomeric form: Novel insights into protein dimerization and multifunctionality. – Biochim. Biophys. Acta, 2015, v. 1854, p. 492-504.

40. Sluchanko N.N., Tugaeva K.V., Faletrov Y.V., Levitsky D.I. High-yield soluble expression, purification and characterization of human steroidogenic acute regulatory protein (StAR) fused to a cleavable Maltose-Binding Protein (MBP). – Protein Expression & Purification, 2016,  v. 119, p. 27-35.

41. Eronina T.B., Mikhaylova V.V., Chebotareva N.A., Makeeva V.F., Kurganov B.I. Checking for reversibility of aggregation of UV-irradiated glycogen phosphorylase b under crowding conditions. – International Journal of Biological Macromolecules. 2016, v. 86, p. 829-839.

42. Borzova V.A., Markossian K.A., Chebotareva N.A., Kleymenov S.Yu., Poliansky N.B., Muranov K.O., Steyn-Margolina V.A., Shubin V.V., Markov D.I., Kurganov B.I. Kinetics of thermal denaturation and aggregation of bovine serum albumin. – PloS ONE, 2016, 11(4): e0153495.

43. Eronina T.B., Mikhaylova V.V., Chebotareva N.A., Makeeva V.F., Kurganov B.I. Checking for reversibility of aggregation of UV-irradiated glycogen phosphorylase b under crowding conditions. – International Journal of Biological Macromolecules, 2016, v. 86, p. 829–839.

44. Eronina T.B., Mikhaylova V.V., Chebotareva N.A., Kurganov B.I. Kinetic regime of thermal aggregation of holo- and apoglycogen phosphorylases b. – International Journal of Biological Macromolecules, 2016, vol. 92, p. 1252-1257.

45. Chebotareva N.A., Roman S.G., Kurganov B.I. Dissociative mechanism for irreversible thermal denaturation of oligomeric proteins. – Biophysical Reviews, 2016, v. 8, p. 397-407.

46. Kara D.A., Borzova V.A., Markossian K.A., Kleymenov S.Y., Kurganov B.I. A change in the pathway of dithiothreitol-induced aggregation of bovine serum albumin in the presence of polyamines and arginine.- International Journal of Biological Macromolecules, 2017, v. 104, Pt A, p. 889-899.

47. Borzova V.A., Markossian K.A., Kleymenov S.Y., Kurganov B.I. A change in the aggregation pathway of bovine serum albumin in the presence of arginine and its derivatives. – Scientific Reports, 2017, v. 21, p. 398

48. Mikhaylova V.V., Eronina T.B., Chebotareva N.A., Kleymenov S.Y., Shubin V.V., Kurganov B.I. A thermal after-effect of UV irradiation of muscle glycogen phosphorylase b. – PLoS One, 2017. v. 12, e0189125.

49. Matyushenko A.M., Artemova N.V., Shchepkin D.V., Kopylova G.V., Nabiev S.R., Nikitina L.V., Levitsky D.I., Bershitsky S.Y. The interchain disulfide cross-linking of tropomyosin alters its regulatory properties and interaction with actin filament. – Biochemical and Biophysical Research Communications, 2017, v. 482, p. 305–309.

50. Matyushenko A.M., Shchepkin D.V., Kopylova G.V., Popruga K.E., Artemova N.V., Pivovarova A.V., Bershitsky S.Y., Levitsky D.I. Structural and functional effects of cardiomyopathy-causing mutations in troponin T-binding region of cardiac tropomyosin. – Biochemistry, 2017, v. 56, p. 250–259.

51. Scellini B., Piroddi N., Matyushenko A.M., Levitsky D.I., Poggesi C., Lehrer S.S., Tesi C. Relaxation properties of myofibrils are compromised by amino acids that stabilize α-tropomyosin. – Biophysical Journal, 2017, v. 112, p. 376–387.

52. Eronina T.B., Mikhaylova V.V., Chebotareva N.A., Borzova V.A., Yudin I.K., Kurganov B.I. Mechanism of aggregation of UV-irradiated glycogen phosphorylase b at a low temperature in the presence of crowders and trimethylamine N-oxide. – Biophysical Chemistry, 2018, v. 232, p. 12-21.

53. Kurganov B.I. Kinetic regime of aggregation of UV-irradiated glyceraldehyde-3-phosphate dehydrogenase from rabbit skeletal muscle. – Biochem. Biophys. Res. Commun., 2018, v. 495, p. 1182-1186.

54. Eronina T.B., Mikhaylova V.V., Chebotareva N.A., Shubin V.V., Kurganov B.I. Effect of ionic strength and arginine on aggregation of UV-irradiated muscle glycogen phosphorylase b. – International Journal of Biological Macromolecules, 2018, v. 118(Pt A), p. 1193-1202.

55. Logvinova D.S., Matyushenko A.M., Nikolaeva O.P., Levitsky D.I. Transient interaction between the N-terminal extension of the essential light chain-1 and motor domain of the myosin head during the ATPase cycle. Biochemical and Biophysical Research Communications, 2018, v. 495, № 1, p. 163-167.

56. Logvinova D.S., Levitsky D.I. Essential light chains of myosin and their role in functioning of the myosin motor. – Biochemistry (Moscow), 2018, v. 83, p. 944–960.

57. Matyushenko A.M., Shchepkin D.V., Kopylova G.V., Bershitsky S.Y., Koubassova N.A., Tsaturyan A.K., Levitsky D.I. Functional role of the core gap in the middle part of tropomyosin. – FEBS Journal, 2018, v. 285, № 5, p. 871–886.

58. Matyushenko A.M., Kleymenov S.Y., Susorov D.S., Levitsky D.I. Thermal unfolding of homodimers and heterodimers of different skeletal muscle isoforms of tropomyosin. – Biophysical Chemistry, 2018, v. 243, p. 1–7.

59. Zamyatnin A.A. Structural–functional diversity of the natural oligopeptides. – Progress in Biophysics & Molecular Biology, 2018, v. 133, p. 1-8.

60. Chebotareva N.A., Eronina T.B., Roman S.G., Mikhaylova V.V., Sluchanko N.N., Gusev N.B., Kurganov B.I. Oligomeric state of αB-crystallin under crowded conditions. – Biochem. Biophys. Res. Commun., 2019, v. 508, p. 1101-1105.

61. Matyushenko A.M., Koubassova N.A., Shchepkin D.V., Kopylova G.V., Nabiev S.R., Nikitina L.V., Bershitsky S.Y., Levitsky D.I., Tsaturyan A.K. The effects of cardiomyopathy-associated mutations in the head-to-tail overlap junction of α-tropomyosin on its properties and interaction with actin. – International Journal of Biological Macromolecules, 2019, v. 125, p. 1266-1274.

62. Matyushenko A.M., Shchepkin D.V., Susorov D.S., Nefedova V.V., Kopylova G.V., Berg V.Y., Kleymenov S.Y., Levitsky D.I. Structural and functional properties of αβ-heterodimers of tropomyosin with myopathic mutations Q147P and K49del in the β-chain. – Biochem. Biophys. Res. Commun., 2019, v. 508(3), p. 934-939.