Research Interests
Physical basis of the structure
of biological molecules and their complexes
From the very beginning
of my scientific career, my research interests have concentrated
on the physical principles of the architecture of biological
macromolecules, proteins, nucleic acids and their complexes,
namely the energetics of formation of their unique three-dimensional
structures. These aims require experimental studies of the conformation
of these molecules under various conditions and measurements
of the energies involved in changes of their structures and
of their association with molecular partners. The problem of
molecular recognition, particularly of DNA by gene regulating
proteins, attracts at the present time rapidly increasing attention.
Its solution largely depends on the extent of information concerning
the energetics of this process. Realization of this program
has required development of a supersensitive calorimetric technique,
microcalorimetry, which is now widely used in many other laboratories.
Except microcalorimetry we are also using extensively various
optical methods: CD, fluorescence anisotropy and florescence
resonance energy transfer (FRET) to investigate the protein
interaction with and changes in their structure resulted from
their association. We are working with various proteins
and their mutants that we construct to solve the problem of
forces responsible for the protein folding and their association
with the partners. In our experiments we are using also
synthetic polypeptides and polynucleotides as models, particularly
in studying protein interactions with their target DNAs.

Figure 1. Transcription factor GCN4-bZIP bound to DNA
Representative
Publications
Dragan, A.I., Hargreaves, V.V., Makeyeva, E.N., and Privalov, P.L. 2007. Mechanisms of activation of interferon regulator factor 3: the role of C-terminal domain phosphorylation in IRF-3 dimerization and DNA binding. Nucleic Acids Res. 35:3525-34.
Crane-Robinson, C., Dragan, A.I., and Privalov, P.L. 2006. The extended arms of DNA-binding domains: a tale of tails. Trends Biochem Sci. 31:547-52.
Samec, J.S., Ell, A.H., Aberg, J.B., Privalov, T., Eriksson, L., and Backvall, J.E. 2006. Mechanistic study of hydrogen transfer to imines from a hydroxycyclopentadienyl ruthenium hydride. Experimental support for a mechanism involving coordination of imine to ruthenium prior to hydrogen transfer. J Am Chem Soc. 128(44):14293-305.
Mushkacheva, G, Rabinovich, E, Privalov, V, Povolotskaya, S, Shorokhova, V, Sokolova, S, Turdakova, V, Ryzhova, E, Hall, P, Schneider, AB, Preston, DL, and Ron, E. 2006. Thyroid abnormalities associated with protracted childhood exposure to (131)i from atmospheric emissions from the mayak weapons facility in Russia. Radiat Res. 166(5):715-22.
Privalov, P.L. and Dragan, A.I. 2006. Microcalorimetry of biological macromolecules.
Biophys Chem (Epub ahead of print).
Privalov, P.L. 2006. Reflections on the origins of microcalorimetry of biopolymers.
Biophys Chem (Epub ahead of print).
Bjelic, S, Karshikoff, A, and Jelesarov, I. 2006. Stability and folding/unfolding kinetics of the homotrimeric coiled coil Lpp-56. Biochemistry. 45(29):8931-9.
Macak, P, Fromager, E, Privalov, T, Schimmelpfennig, B, Grenthe, I, and Wahlgren, U. 2005. Electron transfer in neptunyl(VI)-neptunyl(V) complexes in solution. J Phys Chem A Mol Spectrosc Kinet Environ Gen Theory. 109(22):4950-6.
Fromager, E, Vallet, V, Schimmelpfennig, B, Macak, P, Privalov, T, and Wahlgren, U. 2005. Spin-orbit effects in electron transfer in neptunyl(VI)-neptunyl(V) complexes in solution.
J Phys Chem A Mol Spectrosc Kinet Environ Gen Theory. 109(22):4957-60.
Hargreaves, VV, Makeyeva, EN, Dragan, AI, and Privalov, PL. 2005. Stability and DNA binding ability of the DNA binding domains of interferon regulatory factors 1 and 3. Biochemistry. 44(43):14202-9.
Dragan, A.I., Read, C. M., Makeyeva, E.N ., Milgotina, E.I., Crane-Robinson, C., and Privalov, P.L. 2004. DNA binding and bending by sequence specific HMG boxes: energetic determinants of specificity. J. Mol. Biol. 343 , 371-309.
Dragan, A.I., Frank, L., Liu, Y., Makeyeva, E. N., Crane-Robinson, C. & Privalov, P. L 2004. Thermodynamic signature of GCN4-bZIP binding to DNA indicates the role of water in discriminating between the AP-1 and ATF/CREB sites. J. Mol. Biol . 343 , 865-878.
Dragan, A.I., Liu, Y., Makeyeva, E. N., and Privalov, P.L. 2004. DNA-binding domain of GCN4 induces bending of both the ATF/CREB and AP-1 binding sites of DNA. Nucleic Acids Research , 32 , 5192-5197.
Dragan, A.I., Potekhin S.A., Sivolob, A., Lu, M., and Privalov, P.L. 2004. Kinetics and thermodynamics of the unfolding/refolding of the three-stranded a -helical coiled-coil, Lpp-56. Biochemistry , 43 , 14891-14900.
Dragan, A.I., Liggins, J.R., Crane-Robinson, C., and Privalov, P.L. 2003. The energetics of specific binding of AT-hooks from HMGA1 to target DNA. J. Mol. Biol. 327 , 393-411.
Dragan, A.I., Klass, J., Read, C.M Churchill, E. A., Crane-Robinson, C., and Privalov, P.L. 2003. DNA binding of a non-sequence-specific HMG-D protein is entropy driven with a substantial non-electrostatic contribution. J. Mol. Biol . 327 , 393-411.
Dragan, A.I. Privalov, P.L. 2002. Unfolding of a leucine zipper is not a simple two-state transition. J. Mol. Biol. 321 , 891-908.
Yu, Y. B., Privalov, P. L. & Hodges, R. S. 2001. Contribution of translational and rotational motions to molecular association in aqueous solution. Biophys. J. 81 , 1632-1642.
Privalov, G.P. and Privalov, P.L. 2000. Problems and prospects in the microcalorimetry of biological macromolecules. Methods in Enzymology , 323 , 31-62.
Liggins, J.R. & Privalov, P.L. 2000. Energetics of the specific binding interaction of the first three zinc fingers of the transcription factor TFIIIA with its cognate DNA sequence. Proteins: Struct. Funct. Genetics , 4 , 50-62. |