DYNAMICS AND MECHANISMS OF INTERACTION OF HETERO-HEXAMERIC TIP49a/b COMPLEXES WITH DS-DNA
A.S. Afanasyeva,1, 2, 3, * A.P. Yakimov,2, 3 M.Yu. Grigoriev,4 M.G. Petukhov 2, 3
1 Department of Biophysics, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, 195251,
2 Petersburg Nuclear Physics Institute B. P. Konstantinov NRC "Kurchatov Institute", Gatchina, 188300,
3 Institute of Nanobiotechnology, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, 195251,
and 4 Universite Paul Sabatier, Université de Toulouse, Laboratoire de Biologie Moléculaire Eucaryote, F-31000 Toulouse, France;
* e-mail: arina.afan@gmail.com
Evolutionary conserved TIP49a and TIP49b ATPases belong to the AAA+ superfamily of DNA-dependent ATPases that are involved in many cellular processes such as
chromatin remodeling, regulation of transcription and cell division during mitosis, the maintenance of genome stability, snoRNP biogenesis, and participate in the formation
of active form of telomerase. These proteins are involved in the complex networks of protein-protein interactions and, in spite of high structural similarity, in some cases, can
perform opposite functions. Despite of the variety of their different activities, the exact mechanisms of action of TIP49a and TIP49b are still poorly un-derstood. In this paper,
by means of molecular docking approaches we first modeled the structures of hetero-he-xameric TIP49 complexes with short ds-DNA fragments (20 base pairs with different
GC content) within the central channel of hexameric ring. Using molecular dynamics simulations in the periodic water box (MD) we investigated conformational dynamics and
mechanisms of DNA unwinding activity of these proteins. We shown that: a) the interaction between the positively charged protein loops and DNA within the central channel
of protein ring leads to the partial unwinding of the DNA helix; b) DNA unwinding occurs only in the region within the protein ring, while the terminal parts of DNA outside the
protein complex remain in its initial b-form conformation; c) the presence of ATP in the active sites of protein complex affects both the dynamics and the structure of DNA,
leading to the breakage of some complementary bonds in AT-rich DNA sequences.
Key words:
molecular dynamics, TIP49, structural changes of DNA, hexameric complex
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