Бобик Татьяна Владимировна

Кандидат химических наук

Научный сотрудник (Лаборатория биокатализа)

Эл. почта: bobik_tanya@mail.ru

Избранные публикации

  1. Ponomarenko N., Chatziefthimiou S.D., Kurkova I., Mokrushina Y., Stepanova A., Smirnov I., Avakyan M., Bobik T., Mamedov A., Mitkevich V., Belogurov A., Fedorova O.S., Dubina M., Golovin A., Lamzin V., Friboulet A., Makarov A.A., Wilmanns M., Gabibov A. (2014). Role of κ→λ light-chain constant-domain switch in the structure and functionality of A17 reactibody. Acta Crystallogr. D Biol. Crystallogr. 70 (Pt 3), 708–19 [+]

    The engineering of catalytic function in antibodies requires precise information on their structure. Here, results are presented that show how the antibody domain structure affects its functionality. The previously designed organophosphate-metabolizing reactibody A17 has been re-engineered by replacing its constant κ light chain by the λ chain (A17λ), and the X-ray structure of A17λ has been determined at 1.95 Å resolution. It was found that compared with A17κ the active centre of A17λ is displaced, stabilized and made more rigid owing to interdomain interactions involving the CDR loops from the VL and VH domains. These VL/VH domains also have lower mobility, as deduced from the atomic displacement parameters of the crystal structure. The antibody elbow angle is decreased to 126° compared with 138° in A17κ. These structural differences account for the subtle changes in catalytic efficiency and thermodynamic parameters determined with two organophosphate ligands, as well as in the affinity for peptide substrates selected from a combinatorial cyclic peptide library, between the A17κ and A17λ variants. The data presented will be of interest and relevance to researchers dealing with the design of antibodies with tailor-made functions.

  2. Lomakin Y.A., Zakharova M.Y., Stepanov A.V., Dronina M.A., Smirnov I.V., Bobik T.V., Pyrkov A.Y., Tikunova N.V., Sharanova S.N., Boitsov V.M., Vyazmin S.Y., Kabilov M.R., Tupikin A.E., Krasnov A.N., Bykova N.A., Medvedeva Y.A., Fridman M.V., Favorov A.V., Ponomarenko N.A., Dubina M.V., Boyko A.N., Vlassov V.V., Belogurov A.A. Jr, Gabibov A.G. (2014). Heavy-light chain interrelations of MS-associated immunoglobulins probed by deep sequencing and rational variation. Mol. Immunol. , [+]

    The mechanisms triggering most of autoimmune diseases are still obscure. Autoreactive B cells play a crucial role in the development of such pathologies and, in particular, production of autoantibodies of different specificities. The combination of deep-sequencing technology with functional studies of antibodies selected from highly representative immunoglobulin combinatorial libraries may provide unique information on specific features in the repertoires of autoreactive B cells. Here, we have analyzed cross-combinations of the variable regions of human immunoglobulins against the myelin basic protein (MBP) previously selected from a multiple sclerosis (MS)-related scFv phage-display library. On the other hand, we have performed deep sequencing of the sublibraries of scFvs against MBP, Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), and myelin oligodendrocyte glycoprotein (MOG). Bioinformatics analysis of sequencing data and surface plasmon resonance (SPR) studies have shown that it is the variable fragments of antibody heavy chains that mainly determine both the affinity of antibodies to the parent autoantigen and their cross-reactivity. It is suggested that LMP1-cross-reactive anti-myelin autoantibodies contain heavy chains encoded by certain germline gene segments, which may be a hallmark of the EBV-specific B cell subpopulation involved in MS triggering.

  3. Gasparian M.E., Bobik T.V., Kim Y.V., Ponomarenko N.A., Dolgikh D.A., Gabibov A.G., Kirpichnikov M.P. (2013). Heterogeneous catalysis on the phage surface: Display of active human enteropeptidase. Biochimie 95 (11), 2076–81 [+]