Regulation of muscle contractile activity and small heat shock proteins
Group of Professor N.B. Gusev has worked in the Department of Biochemistry for more than 25 years. Three main lines of investigation are performed in the group. The first line of investigation, started in mid-1980s, deals with analysis of the structure and properties of proteins involved in regulation of contractile activity of different muscle (troponins I and T, caldesmon, calponin). The structure of troponin complex regulating contractile activity of skeletal and cardiac muscle was investigated. A new isoform of cardiac troponin T was detected and a new enzyme catalyzing phosphorylation of troponin T was described. The structure and properties of caldesmon and calponin participating in regulation of smooth muscle contraction were investigated. Protein kinases phosphorylating and regulating caldesmon and calponin were analyzed. Different Ca-binding proteins regulating smooth muscle contractility were characterized and calmodulin-binding sites of caldesmon were mapped.
The second direction of investigation deals with the investigation of universal adapter protein 14-3-3, which is able to recognize and interact with different phosphorylated target proteins. The effect of mutations mimicking phosphorylation on ligand-binding properties and 14-3-3 structure was thoroughly investigated. It has been shown that tau protein involved in the regulation of cytoskeleton of nervous cells contains a number of phosphorylated sites which are recognized by 14-3-3. In phosphorylated state, HspB6 forms tight complexes with 14-3-3 and by this means, can indirectly participate in the regulation of contractile activity of non-muscle cells and smooth muscle where important actin-binding protein, cofilin, plays a crucial regulatory role.
The third direction of investigation deals with the investigation of the structure and properties of human small heat shock proteins. Recombinant human small heat shock proteins, HspB1, HspB5, HspB6 and HspB8 were obtained. The structure and chaperone-liked activity of these proteins were determined. Investigation of the structure and properties of mutant small heat shock proteins which expression is associated with different human congenital diseases were started. The structure and properties of heterooligomeric complexes formed by different small heat shock proteins were investigated and the sites involved in inter-subunit contacts were mapped.
Fifteen PhD theses were prepared in the group. The former postgraduate student and members of the group are successfully working in different scientific and medical institutes in Russia and abroad (Germany, Switzerland and USA). Investigations performed in the group were supported by grants by the Russian Foundation for Basic Research, INTAS and Wellcome Trust. The students and postgraduate students which were working in the group were awarded a stipendium of S.E. Severin (I.S. Chernik, A.E. Glukhova, N.N. Sluchanko, E.V. Mymrikov, V.V. Nefedova), special prizes for young scientists (N.V. Bogatcheva, O.O. Panasenko, I.S. Chernik), special stipendiums for post-graduate students and young scientists of the Moscow State University (M.V. Kim, A.A. Shemetov, E.V. Mymrikov, N.N. Sluchanko, P.N. Datskevich), stipendium of the President of Russian Federation for postgraduate students (E.V. Mymrikov, N.N. Sluchanko), golden medal of the Russian Academy of sciences for young scientists (N.N. Sluchanko) and premiums of the Russian Academy of Sciences and Medical Sciences (A.B. Dobrovolsky, V.V. Risnik, N.B. Gusev).
Key publications
- Mymrikov EV, Seit-Nebi AS, Gusev NB. Large potentials of small heat shock proteins. Physiol Rev. 2011; 91(4):1123-59.
- Nefedova VV, Sudnitsyna MV, Strelkov SV, Gusev NB. Structure and properties of G84R and L99M mutants of human small heat shock protein HspB1 correlating with motor neuropathy. Arch Biochem Biophys. 2013;538(1):16-24.
- Muranova LK, Weeks SD, Strelkov SV, Gusev NB. Characterization of Mutants of Human Small Heat Shock Protein HspB1 Carrying Replacements in the N-Terminal Domain and Associated with Hereditary Motor Neuron Diseases. PLoS One. 2015;10(5):e0126248.
- Sluchanko NN, Beelen S, Kulikova AA, Weeks SD, Antson AA, Gusev NB, Strelkov SV. Structural Basis for the Interaction of a Human Small Heat Shock Protein with the 14-3-3 Universal Signaling Regulator. Structure. 2017; 25(2):305-316.
- Weeks SD, Muranova LK, Heirbaut M, Beelen S, Strelkov SV, Gusev NB. Characterization of human small heat shock protein HSPB1 α-crystallin domain localized mutants associated with hereditary motor neuron diseases. Sci Rep. 2018; 8(1):688.
Group members:
| Group leader | professor N.B. Gusev |
| Researcher | L.K. Muranova |
| Assistant Professors | A.S. Ryzhavskaya |
| Teaching master | I.P. Evdokimova |
| Post-graduate student | V.M. Shatov |
| Graduate student, laboratory assistant |
A.V. Slushchev |
